IMMUNOLOGY TEXTBOOK - Mercury Podillia 2013

BASIC PRINCIPLES OF IMMUNODEFICIENCY TREATMENT

Characteristics of Immunomodulators

Preprations of bacterial and fungal origin

Vaccines as immunomodulators. Vaccines derived from opportunistic Bacteria not only enhance resistance to specific pathogens but also exert a potent nonspecific immunomodulating and stimulating effect. This is attributed to the presence of lipopolysaccharides, Proteins A and M, and other substances that act as strong immune activators and function as adjuvants. An essential prerequisite for prescribing lipopolysaccharide-based Immunomodulatory therapy is an adequate level of target Cells (i.e., absolute counts of neutrophils, monocytes, and lymphocytes).

Resibron contains a bacterial lysate of: St. aureus, Str. pyogenes, Str. viridans, Klebsiella pneumoniae, Klebsiella ozaenae, Haemophilus influenzae, Neisseria catarrhalis, Diplococcus pneumoniae. The drug induces dendritic Cell maturation, increases The production of Immune Response mediators, triggers the response of specific immune defense factors, and enhances the Synthesis of specific secretory IMMUNOGLOBULINS—sIgA and sIgM. It is indicated for acute, subacute, recurrent, and chronic infections of the upper and lower respiratory tracts (rhinitis, sinusitis, laryngitis, pharyngitis, tracheitis, Bronchitis, Bronchiectasis). Available in sublingual tablets. The recommended dosage is 1 tab. daily under the Tongue for a 10-day course. For prophylactic purposes, take 1 tab. daily in 10-day courses over 3 months.

Broncho-Munal is a lyophilized bacterial lysate (Str. pneumoniae, H. influenzae, Str. viridans, Str. pyogenes, Moraxella catarrhalis, S. aureus, K. pneumoniae, and K. ozaenae). It increases the counts of T-lymphocytes and IgG, IgM, sIgA Antibodies, IL-2, and tumor necrosis factor; it is used in the Treatment of Upper Respiratory Tract infectious diseases (bronchitis, rhinitis, tonsillitis). Each capsule contains 0.007 g of lyophilized bacteria, with 10 capsules per pack. The standard dosage is 1 capsule daily for 10 days per month over a 3-month period. Children are prescribed Broncho-Munal II, which contains 0.0035 g of bacteria per capsule. It should be taken in the morning on an empty Stomach. Possible side effects include dyspeptic symptoms, diarrhea, and epigastric pain.

Ribomunyl contains immunomodulating agents represented by a combination of bacterial Ribosomes (Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae) and membrane Proteoglycans of K. pneumoniae. It is prescribed as 1 tablet 3 times a day or 3 tablets taken together in the morning on an empty stomach: During the first month—4 days a week for 3 weeks; over the subsequent 5 months—4 days at the beginning of each month. It builds Immunity against infectious agents and ensures prolonged remission in Chronic bronchitis, rhinitis, tonsillitis, and otitis media.

Imudon (a tablet containing a lyophilized mixture of bacteria: lactobacilli, streptococci, enterococci, staphylococci, klebsiellae, corynebacteria pseudodiphtheriticum, fusiform bacteria, Candida albicans) is used in dentistry for periodontitis, stomatitis, gingivitis, and other inflammatory conditions of the oral mucosa. The recommended dose is 8 tablets per day (1-2 tablets every 2-3 hours); the tablet should be kept in the Mouth until completely dissolved.

IRS-19 is a metered-dose nasal spray (60 doses, 20 ml) containing a bacterial lysate (pneumococcal diplococci, streptococci, staphylococci, Neisseria, Klebsiella, Moraxella, Haemophilus influenzae, etc.). It stimulates phagocytosis and elevates the levels of Lysozyme and sIgA. It is used for rhinitis, pharyngitis, tonsillitis, bronchitis, Bronchial Asthma with rhinitis, and otitis media. The regimen involves 2-5 sprays per day into each nostril until the infection resolves.

Bacterial and Yeast substances

Sodium nucleinate. This nucleic acid sodium salt preparation is obtained by hydrolyzing yeast cells followed by purification. It represents an unstable mixture of 5-25 types of NUCLEOTIDES. It exhibits pleiotropic stimulating activity on immune cells: it enhances the phagocytic activity of micro- and macrophages and the production of active oxygen radicals by these cells, thereby boosting the bactericidal action of phagocytes and increasing antitoxic antibody titers. It is administered orally in tablets at the following single doses: children in their 1st year of life—0.005-0.01 g; ages 2 to 5—0.015-0.02 g; ages 6 to 12—0.05-0.1 g. The daily dose consists of two to three single doses calculated According to the patient's age. Adults receive no more than 0.1 g per single dose, up to 4 times a day.

Pyrogenal. This preparation is derived from a culture of Pseudomonas aeruginosa. It has low toxicity but induces fever and transient leukopenia followed by leukocytosis. It exerts a particularly powerful effect on the phagocytic cell system, which is why it is frequently used in the combined therapy of protracted and chronic Inflammatory Diseases of the respiratory tract and other sites. It is administered intramuscularly. Injections are not recommended for children under 3 years of age. For children over 3, the dose ranges from 3 to 25 mcg (5-15 minimum pyrogenic doses, MPD) per injection depending on age, not exceeding 250-500 MPD. For adults, the usual dose is 30-150 mcg (25-50 MPD) per injection, with a maximum of 1000 MPD. The course of therapy includes 10 to 20 injections, requiring monitoring of peripheral Blood counts and immune status.

The pyrogen test is a diagnostic Procedure used in leukopenic states to stimulate the emergency release of immature granulocyte forms from cellular depots. The drug is administered at a dose of 15 MPD per 1 m2 of body surface area. An alternative calculation formula is 0.03 mcg per 1 kg of body weight. The test is contraindicated during Pregnancy, acute febrile states, and leukopenias of autoimmune origin.

Yeast preparations contain Nucleic Acids and a complex of natural Vitamins and Enzymes. They are typically used for bronchitis, furunculosis, slow-healing ulcers and wounds, anemia, and during convalescence after severe illnesses. Up to 5-10 g of yeast is mixed with 30-50 ml of warm Water, ground, and kept in a warm place for 15-20 minutes until foam forms. The mixture is stirred and drunk 15-20 minutes before meals 2-3 times a day for 3-4 weeks. The clinical effect appears within a week, while the immunological effect manifests later. To reduce dyspepsia, the preparation can be diluted with milk or tea.

Synthetic immunomodulators

Licopid is a semisynthetic drug belonging to muramyl dipeptides, which are structurally similar to bacterial components. It is a fragment of the Introduction/37.html">Bacterial Cell wall obtained from Micrococcus lysodeikticus.

The drug enhances the body's overall resistance to pathogenic factors, primarily through the activation of phagocytic immune cells (neutrophils and macrophages). In cases of depressed hematopoiesis—for instance, induced by Chemotherapy or radiation—the administration of Licopid leads to the restoration of neutrophil counts. Licopid also activates T- and B-lymphocytes.

Indications: acute and chronic purulent-inflammatory diseases; acute and chronic respiratory disorders; human papillomavirus cervical lesions; vaginitis; acute and chronic viral infections (ophthalmoherpes, herpetic infections, herpes zoster); Pulmonary Tuberculosis; trophic ulcers; psoriasis; and immunoprophylaxis of common colds.

Treatment courses are prescribed depending on the specific condition. For chronic respiratory infections (bronchitis) in the acute stage: 1-2 tablets (1-2 mg) sublingually for 10 days. For protracted recurrent infections: 1 tablet (10 mg) once daily for 10 days. Pulmonary tuberculosis: 1 tablet (10 mg) sublingually once daily in 3 cycles of 7 days with 2-week intervals (2 packs of 10 mg per course). Herpes (mild forms): 2 tablets (1 mg x 2) 3 times daily sublingually for 6 days (4 packs of 1 mg per course); for severe forms: 1 tablet (10 mg) 1-2 times daily orally for 6 days (1-2 packs of 10 mg per course). Children are prescribed 1 mg tablets.

Contraindicated during pregnancy. A body Temperature rise of up to 38 °C, occasionally occurring after administration of the drug, is not a contraindication.

Reosorbilact is used for detoxification. It may exert an immunomodulating effect in the treatment of chronic obstructive pulmonary disease, rheumatism, and intestinal infections. It is administered to adults at 100-200 ml and to children at 2.5-5 ml/kg via intravenous drip (40-80 drops per minute) every other day.

Dibazole (Dibazolum) is a vasodilator and hypotensive agent. The drug exhibits adaptogenic and interferonogenic effects, enhances the synthesis of proteins and nucleic acids, and promotes the expression of IL-2 and receptors on T-helper cells. It is used in acute infections (bacterial and viral). The combination of Dibazole and Licopid is considered optimal. It is prescribed in 0.02 g tablets (single dose up to 0.15 g), or as 1, 2, or 5 ml ampoules of 0.5% or 1% solution for 7-10 days. For young children—0.001 g/day; up to 1 year—0.003 g/day; preschool age—0.0042 g/day.

Blood pressure should be monitored, particularly in adolescents, in whom Dibazole may cause vascular tone regulation disorders.

Dimexide (dimethyl sulfoxide) is available in 100 ml bottles as a liquid with a specific odor, possessing unique tissue-penetrating ability and a pH of 11. It exhibits anti-inflammatory, anti-edematous, bactericidal, and immunomodulatory effects. It stimulates phagocytes and lymphocytes. In rheumatology, a 15% solution is used as joint compresses for rheumatoid Arthritis. It is also utilized for purulent-septic and bronchopulmonary diseases. The course typically consists of 5-10 Applications.

Isoprinosine (groprinosine) is a complex of inosine and raceturate in a 1:3 ratio. It stimulates phagocytic cells and lymphocytes, promoting the production of cytokines and IL-2, which significantly alters the functional activity of peripheral blood lymphocytes and their specific immunological Functions: it induces the differentiation of 0-cells into T-lymphocytes and enhances The activity of cytotoxic lymphocytes. It exhibits low toxicity and is well tolerated by patients. Possessing a pronounced interferonogenic effect, it is used to treat acute and prolonged viral infections (herpes, measles, hepatitis A and B, etc.). It also stimulates mature B-cells. It is administered orally in tablets (1 tab. 500 mg) at a dose of 50-100 mg per kg of body weight per day. The daily dose is divided into 4-6 intakes over a 5-7 day course. Indications include secondary immunodeficiency disorders, particularly in herpetic infections.

Imunofan (Imunofan) is a hexapeptide (arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-Arginine) with immunoregulatory, detoxifying, and hepatoprotective properties that inactivates free radicals and peroxide compounds.

The drug's effect develops within 2-3 hours and lasts for up to

4 months. It normalizes Lipid Peroxidation, inhibits the synthesis of arachidonic acid, leading to lowered blood Cholesterol levels and reduced production of inflammatory mediators. Within 2-3 days, it enhances phagocytosis. The immunomodulatory effect of the drug manifests within 7-10 days, promoting T-lymphocyte proliferation, increasing IL-2 production, and stimulating antibody and interferon synthesis. The ampoules contain 1 ml of a 0.005% solution (packaged in boxes of 5). It is administered subcutaneously or intramuscularly daily or every 1-4 days, with a course consisting of 5-15 injections. For herpes, cytomegalovirus infection, Toxoplasmosis, chlamydia, and pneumocystosis, the regimen is 1 injection every 48 hours for a total of 10-15 injections.

Galavit (Galavit) is an aminophthalhydrazide derivative with anti-inflammatory and immunomodulatory activity. It is recommended for secondary immune deficiencies and chronic, recurrent, sluggish infections across various Organs and localizations. It is administered intramuscularly at an initial dose of 200 mg, followed by 100 mg 2-3 times daily until intoxication subsides or inflammation ceases. A maintenance course is administered every 2-3 days. It has been validated for furunculosis, intestinal infections, adnexitis, herpes, Cancer chemotherapy, and as an inhalation therapy for chronic bronchitis.

Polyoxidonium is a next-generation synthetic immunomodulator—an N-oxidized polyethylenepiperazine derivative characterized by a broad pharmacological spectrum and high immunostimulatory activity. It has been shown to exert a predominant effect on the phagocytic link of the immunity.

It activates phagocytes and enhances the microbicidal capacity of macrophages against pathogens; stimulates reticuloendothelial system cells to capture, phagocytose, and clear foreign microparticles from circulating blood; increases the adhesion of Blood Leukocytes and their ability to generate reactive oxygen species upon contact with opsonized microbial fragments; promotes cooperative T- and B-cell interactions; enhances the body's natural resistance to infections; normalizes The Immune System in secondary immunodeficiencies; and exhibits antitumor properties. Polyoxidonium is administered intramuscularly once daily in doses ranging from 6 to 12 mg. The treatment course consists of 5 to 7 injections, given either every other day or according to the following schedule: days 1, 2, 5, 8, 11, and 14.

Methyluracil stimulates leukopoiesis, enhances cell proliferation and differentiation, and increases antibody production. Single oral doses are recommended as follows: for children aged 1 to 3 years—0.08 g; aged 3 to 8 years—0.1-0.2 g; aged 8 to 12 years and adults—0.3-0.5 g. Patients receive 2-3 single doses per day over a 2-3 week course. In secondary immunological deficiency, it is used in patients with moderate cytopenic conditions.

Theophylline stimulates suppressor T-cells at a dose of 0.15 mg three times daily for 3 weeks. This results not only in a reduction of B-cell counts but also in the suppression of their functional activity. It can be utilized in the treatment of autoimmune diseases and autoimmune syndromes associated with immunodeficiency. However, its primary clinical indication is the treatment of bronchial asthma due to its bronchodilator effect.

Famotidine, an H2-histamine receptor blocker, suppresses T-suppressors, stimulates T-helpers, and promotes the expression of IL-2 receptors alongside immunoglobulin synthesis.

Interferon Inducers stimulate the production of endogenous interferon.

Amiksin stimulates the production of alpha, beta, and gamma interferons, enhances antibody formation, and exhibits antibacterial and antiviral effects. It is used for the treatment of hepatitis A and enteroviral infections (1 tablet of 0.125 g for adults or 0.06 g for children daily for 2 days, followed by a 4-5 day break, with a total course of 2-3 weeks), as well as for the prophylaxis of viral infections (Influenza, acute respiratory infections, ARVI) at 1 tablet once a week for 3-4 weeks. It is contraindicated during pregnancy and in the presence of Liver or Kidney diseases.

Arbidol is an antiviral agent that inhibits influenza A and B Viruses, possesses interferon-inducing activity, and stimulates humoral and cellular immune responses. Available in 0.1 g tablets. For the treatment of viral infections, it is prescribed at 0.1 g three times daily before meals for 3-5 days, followed by 0.1 g once a week for 3-4 weeks. For children aged 6-12 years, 0.1 g is administered every 3-4 days for 3 weeks as a prophylactic measure during influenza epidemics; for treatment, children receive 0.1 g 3-4 times daily for 3-5 days. It is contraindicated in patients with cardiovascular, hepatic, or renal pathologies.

Neovir induces the synthesis of alpha-interferon, activates stem cells, NK cells, T-lymphocytes, and macrophages, and lowers TNF-α levels. During the acute phase of herpetic infection, 3 injections of 250 mg are administered at 16-24 hour intervals, followed by 3 more injections at 48-hour intervals. During the inter-relapse period, 1 injection of 250 mg is given weekly for a month. For urogenital chlamydia, 5-7 injections of 250 mg are administered at 48-hour intervals, with antibiotic therapy initiated on the day of the second injection. It is supplied as a sterile injection solution in 2 ml ampoules containing 250 mg of the active substance in a physiologically compatible buffer, packaged in boxes of 5.

Cycloferon is available as a 12.5% injection solution (2 ml), 0.15 g tablets, and a 5% ointment (5 ml). It stimulates the production of α, β, and γ-interferons (up to 80 IU/ml) and increases CD4+ and CD4+ T-lymphocyte levels in HIV infection. It is recommended for herpes, cytomegalovirus infection, hepatitis, HIV, multiple sclerosis, PEPTIC ULCER DISEASE, and rheumatoid arthritis. The single dose is 0.25-0.5 g administered intramuscularly or intravenously on days 1, 2, 4, 6, 8, 11, 14, 17, 20, 23, 26, and 29. For children, the dosage is 6-10 mg/kg/day intravenously or intramuscularly. Tablets are taken at 0.3-0.6 g once daily for influenza and respiratory infections; the ointment is used topically for herpes, vaginitis, and urethritis.

Kagocel is a synthetic agent based on carboxymethylcellulose and the polyphenol gossypol. It induces the synthesis of α- and β-interferons, which are produced for up to a week following a single administration. Available in 12 mg tablets. For the treatment of influenza and ARVI in adults, the regimen is 2 tablets three times daily for the first two days, followed by 1 tablet three times daily for the next two days (total course: 18 tablets over 4 days). Prophylaxis of respiratory viral infections in adults is carried out in 7-day cycles: 2 tablets once daily for two days, followed by a 5-day break, repeating the cycle for a duration ranging from one week to several months. For the treatment of herpes in adults, 2 tablets are prescribed three times daily for 5 days (total course: 30 tablets). For treating influenza and ARVI in children aged 6 years and older, 1 tablet is given three times daily for the first two days, followed by 1 tablet twice daily for the next two days (total course: 10 tablets over 4 days).

Imunofan and dibazol (see above) also function as interferonogens.

Dipyridamole (curantil) is a vasodilator administered at 0.05 g twice daily with a 2-hour interval once a week; it elevates gamma-interferon levels and AIDS in treating viral infections.

Anaferon contains low doses of antibodies to gamma-interferon, granting it immunomodulatory properties. It is used for upper respiratory viral infections (influenza, ARVI) at 5-8 tablets on the first day, followed by 3 tablets daily from the 2nd to the 5th day. For prophylaxis, 1 tablet (0.3 g) is taken daily for 1-3 months.

Preparations derived from cells and Organs of the immune system

Thymic Peptides and Hormones. A crucial characteristic of thymic peptides (originating from epithelioid and stromal cells, Hassall's corpuscles, thymocytes, etc.) as hormones is the short-term and short-range nature of their action on target cells, which dictates therapeutic tactics. Therapeutic agents are obtained through various Methods from animal Thymus extracts. Thymic peptides share a group-wide property of enhancing the differentiation of lymphoid system cells, not only altering lymphocyte functional activity but also inducing the secretion of cytokines, such as IL-2.

Indications for prescribing this group of drugs include clinical and laboratory signs of T-cell immunity deficiency: infectious or other syndromes associated with immunological insufficiency; lymphopenia; a reduced absolute count of T-lymphocytes; a lowered CD4+/CD8+ lymphocyte ratio; depressed proliferative responses to mitogens; and impaired delayed-type hypersensitivity Skin reactions, among others.

Thymic deficiency can be acute or chronic. Acute thymic deficiency develops during intoxications, physical or psycho-emotional stress, and against the Background of severe acute infectious processes. Chronic deficiency characterizes T-cell and combined immunodeficiency forms. Thymic deficiency should not be corrected with general immunostimulants; rather, it requires replacement therapy with thymic Peptide Hormones.

Replacement therapy for acute thymic deficiency typically requires a short course of thymic peptides in a loading regimen alongside symptomatic care. Chronic thymic deficiency is managed with regular courses of thymic peptides. Usually, the drugs are administered in a loading regimen for the first 3-7 days, followed by maintenance therapy.

Congenital forms of T-cell immunological deficiency are nearly unresponsive to thymic factors, generally due to genetically determined defects in target cells or mediator production (e.g., IL-2 and IL-3). Acquired immunodeficiencies respond well to thymic factors provided the genesis of the immunodeficiency stems from thymic deficiency and the resulting immaturity of T-cells. However, thymic peptides do not correct other T-lymphocyte defects (such as enzymatic deficiencies).

Thymalin is a complex of calf thymus peptides. The lyophilized powder in 10 mg vials is dissolved in 1-2 ml of isotonic sodium chloride solution. It is administered intramuscularly to adults at 5-20 mg (30-100 mg per course), to children under 1 year at 1 mg; ages 4-6 at 2-3 mg; ages 4-14 at 3.5 mg over a period of 3-10 days. It is recommended for acute and chronic viral and bacterial infections, Burns, ulcers, infectious bronchial asthma, and immunodeficiency-associated disorders.

Tactivin is a complex of calf thymus Polypeptides, available in 1 ml vials of a 0.01% solution. For chronic nonspecific lung diseases, the optimal dose of Tactivin is 1-2 mcg/kg. The drug is administered subcutaneously at 1 ml (100 mcg) for 5 days, followed by once a week for 1 month. Subsequently, 5-day monthly maintenance courses are administered. It is indicated for purulent-septic processes, Lymphocytic Leukemia, ophthalmoherpes, tumors, psoriasis, multiple sclerosis, and immunodeficiency-associated conditions.

Thymostimulin is a complex of bovine thymus polypeptides administered intramuscularly at a dose of 1 mg per 1 kg of body weight for 7 days, then 2-3 times a week. This dosing regimen was used in the treatment of combined forms of primary immunodeficiency. The best clinical response is observed in patients with functional defects in cellular immunity effectors. Allergic reactions to the drug are possible.

Zadaxin (thymosin alpha-1) induces markers of mature T-Cell Differentiation on lymphocytes isolated from the Bone Marrow of adult thymectomized mice, as well as post-diffusive activity toward the induction of lymphokines and lymphokine receptors on peripheral blood lymphocytes. It enhances T-cell function by increasing the efficiency of T-cell maturation and their ability to produce cytokines such as interferon-gamma (IFN-g), interleukin-2 (IL-2), and interleukin-3 (IL-3) following activation by mitogens or Antigens, and it regulates and upregulates the expression of the high-affinity IL-2 receptor. In addition, thymosin alpha-1 increases natural killer cell activity and enhances the antibody response to T-cell-dependent antigens. Thymosin alpha-1 is prescribed for the treatment of chronic hepatitis B and C, including as part of combination therapy with interferon.

The drug is administered subcutaneously at 1.6 ml (therapeutic dose of 900 mcg/m2) twice a week, with 3-4 days between injections, for a course of 6-12 months. For patients with a body weight of less than 40 kg, the dose is 40 mcg/kg. Zadaxin can be used either as monotherapy or in combination with interferon (according to the prescribed dose and schedule for interferon).

Thymulin is a polypeptide circulating in the blood and secreted by the thymic epithelium. The drug enhances the functional activity of T-lymphocytes. In high doses, it stimulates T-suppressors, while in low doses, it stimulates T-helpers and T-effectors. The greatest efficacy is achieved with subcutaneous administration of 5 mcg daily for 5-10 days.

Blood and Immunoglobulin Products

Passive, substitution immunotherapy encompasses a group of Methods based on the external administration of preformed immunological factors to the patient. In clinical practice, Three types of human immunoglobulin preparations are used: native plasma, intramuscular immunoglobulin, and intravenous immunoglobulin.

Autologous hemotransfusion serves as an alternative to allogeneic blood transfusion. For elective surgeries, early autologous blood collection is recommended (Schander, 1999) along with the administration of Erythropoietin once a week at a dose of 400 IU/kg for 3 weeks, as well as recombinant stimulators of leukopoiesis (GM-CSF) and IL-11, which stimulates thrombopoiesis.

Leukocyte mass is used as a replacement therapy for immunodeficiency states affecting the phagocytic system. The dose of leukocyte mass is 3-5 ml per 1 kg of body weight.

Stem cells—both autologous and allogeneic, derived from bone marrow or blood—are capable of restoring the functions of organs and Tissues through differentiation into mature cells.

Native Blood Plasma (liquid or frozen) contains at least 6 g of total protein per 100 ml, including 50% albumin (40-45 g/l), 45% alpha1-globulin, 8.5% alpha2-globulin (9-10 g/l), 12% beta-globulin (11-12 g/l), and 18% gamma-globulin (12-15 g/l). It may contain cytokines, ABO antigens, and soluble receptors. It is supplied in vials or plastic bags of 50-250 ml. Native plasma should be used on the day of its preparation (no later than 2-3 hours after Separation from blood). Frozen plasma can be stored at temperatures of -25 °C and below for up to 90 days. At a temperature of -10 °C, the storage life is up to 30 days.

Plasma transfusion is performed taking into account blood group compatibility (ABO). At the beginning of the transfusion, a biological test must be performed, and if any signs of a reaction are detected, the transfusion should be stopped.

Dry (lyophilized) plasma is not suitable for the immunotherapy of antibody deficiency syndromes due to a reduction in its therapeutic value resulting from the Denaturation of some unstable protein components, a significant content of polymeric and aggregated IgG, and high pyrogenicity.

Intravenous Immunoglobulins

Intravenous immunoglobulins (IVIG) are safe regarding the transmission of viral infections, contain a sufficient amount of IgG3 responsible for virus neutralization, and possess Fc-fragment activity. Indications for use:

1. Conditions for which the efficacy of IVIG is well-established:

- Primary immunodeficiencies (X-linked agammaglobulinemia; common variable immunodeficiency; transient hypogammaglobulinemia of infancy; immunodeficiency with hyper-IgM; immunoglobulin G subclass deficiencies; antibody deficiency with normal immunoglobulin levels; severe combined immunodeficiencies of all types; Wiskott-Aldrich syndrome; ataxia-telangiectasia; short limb dwarfism; X-linked lymphoproliferative syndrome).

- secondary immunodeficiencies: hypogammaglobulinemia; Prevention of infections in chronic lymphocytic leukemia; prevention of cytomegalovirus infection in allogeneic bone marrow and other organ transplantation; graft-versus-host disease in allogeneic bone marrow transplantation; Kawasaki disease; pediatric AIDS; Guillain-Barré syndrome; chronic demyelinating inflammatory polyneuropathies; acute and chronic immune thrombocytopenic purpura, particularly in children and associated with HIV infection; autoimmune neutropenia.

2. Conditions for which IVIG is likely effective: malignancies with antibody deficiency; prevention of infections in multiple myeloma; protein-losing enteropathies accompanied by hypogammaglobulinemia; Nephrotic Syndrome with hypogammaglobulinemia; neonatal Sepsis; myasthenia gravis; bullous pemphigoid; coagulopathy with a factor VIII inhibitor; autoimmune hemolytic anemia; neonatal auto- or isoimmune thrombocytopenic purpura; post-infectious thrombocytopenic purpura; antiphospholipid antibody syndrome; multifocal neuropathies; hemolytic uremic syndrome; systemic juvenile arthritis, Spontaneous Abortion (antiphospholipid syndrome); Henoch-Schönlein purpura; severe IgA nephropathy; steroid-dependent bronchial asthma; chronic sinusitis; viral infections (Epstein-Barr, respiratory syncytial, parvovirus, adenovirus, cytomegalovirus, etc.); bacterial infections; multiple sclerosis; hemolytic anemias; viral gastritis; Evans syndrome.

3. Conditions for which IVIG may potentially be effective: intractable seizures; systemic lupus erythematosus; dermatomyositis, eczema; rheumatoid arthritis, burn disease; Duchenne muscular dystrophy; Diabetes Mellitus; heparin-induced thrombocytopenic purpura; necrotizing enterocolitis; retinopathy; Crohn's disease; multiple trauma, recurrent otitis media; psoriasis; Peritonitis; meningitis; meningoencephalitis.

The MECHANISM OF ACTION of IgG involves both specific and non-specific effects. The specific effect is related to the action of a small number of constitutively present antibodies, while the non-specific effect is related to immunomodulation. Both effects are typically mediated via leukocyte Fc receptors. By binding to leukocyte Fc receptors, immunoglobulins activate their functions during infections—such as phagocytosis—and conversely, suppress them in allergies. If antibodies are present among the immunoglobulin molecules, they can opsonize bacteria or neutralize viruses.

Features of the clinical application of IVIG. There are several therapeutic and prophylactic approaches for immunoglobulin administration: replacement therapy in immunodeficiencies complicated by infection; immunotherapy in patients with severe infections (sepsis); and suppressive immunotherapy in autoallergic and allergic diseases.

Hypogammaglobulinemia is commonly observed in children with active bacterial infections. In such cases, immunotherapy should be administered in a saturation regimen, concurrently with active antimicrobial chemotherapy. Transfusions of native (fresh or cryopreserved) plasma are administered at a single dose of 15-20 ml/kg of body weight.

IVIG is administered at a daily dose of 400 mg/kg intravenously by drip or infusion at 1 ml/kg/h for premature infants and 4-5 ml/kg/h for full-term infants. For premature infants with a body weight of less than 1500 g and an IgG level of 3 g/l or lower, IVIG is administered for infection prophylaxis. In immunodeficiencies with low blood IgG levels, IVIG is administered until the blood IgG concentration reaches at least 4-6 g/l. In severe purulent-inflammatory diseases, it is administered daily for 3-5 injections or every other day up to 1-2.5 g/kg. In the initial period, intervals between infusions can be 1-2 days, extending up to 7 days towards the end. 4-5 administrations are usually sufficient, meaning that over 2-3 weeks the patient receives an average of 60-80 ml of plasma or 0.8-1.0 g of IVIG per 1 kg of body weight. Over the course of a month, no more than 100 ml of plasma or 1.2 g of IVIG per 1 kg of the patient's body weight is transfused.

After the resolution of acute infectious symptoms in a child with hypogammaglobulinemia, as well as once IgG levels reach at least 400–600 mg/dL, maintenance replacement immunotherapy should be initiated. Clinically effective resolution of focal infections in children correlates with pre-infusion levels above 200 mg/dL (corresponding to a post-infusion level above 400 mg/dL the day following plasma transfusion). This requires monthly administration of 15–20 mL/kg body weight of native plasma or 0.3–0.4 g/kg of IVIG. To achieve the best clinical outcome, prolonged and regular replacement therapy is necessary. A gradual increase in the thoroughness of chronic infection focus eradication is observed over 3–6 months following the completion of the immunotherapy course. This effect reaches its maximum after 6–12 months of continuous replacement immunotherapy.

Intraglobin is an IVIG preparation containing 50 mg of IgG and approximately 2.5 mg of IgA per 1 mL, used for immunodeficiencies, infections, and autoimmune diseases.

Pentaglobin is an IgM-enriched IVIG containing: IgM — 6 mg, IgG — 38 mg, and IgA — 6 mg per 1 mL. It is used for sepsis, other infections, and immunodeficiency: for newborns, 1 mL/kg/hour, 5 mL/kg daily for 3 days; for adults, 0.4 mL/kg/hour, then 0.4 mL/kg/hour, followed by continuous infusion at 0.2 mL/kg up to 15 mL/kg/hour, over 72 hours — 5 mL/kg for 3 days, with a repeated course if necessary.

Octagam is an IVIG containing 50 mg of Plasma Proteins per 1 mL, of which 95% is IgG; less than 100 mcg of IgA, and less than 100 mcg of IgM. It closely resembles native blood plasma IgG, with all IgG subclasses present. Indications include congenital agammaglobulinemia, variable and combined immunodeficiencies, thrombocytopenic purpura, Kawasaki disease, and bone marrow transplantation.

In immunodeficiency, it is administered to achieve a blood plasma IgG level of 4–6 g/L. The initial dose is 400–800 mg/kg, followed by 200 mg/kg every 3 weeks. To achieve an IgG level of 6 g/L, it is necessary to administer 200–800 mg/kg per month. Blood IgG levels are measured for monitoring purposes.

For the treatment and prevention of infections, IVIG dosages depend on The Nature of the infectious process. As a rule, it should be administered as early as possible. In cytomegalovirus (CMV) infection, the dose should be 500 mg/kg weekly for 12 weeks, because the half-life of the IgG3 subclass responsible for virus neutralization is 7 days, and clinical infection manifests between the 4th and 12th weeks post-infection. Antiviral drugs with a synergistic effect are prescribed concurrently.

To prevent neonatal sepsis in preterm infants weighing from 500 to 1750 g, it is recommended to administer 500 to 900 mg/kg/day of IgG to maintain its concentration at no less than 800 mg/kg, under the monitoring of blood IgG levels. The elevation in IgG levels persists on average for 8–11 days post-administration. Administration of IgG to pregnant women after 32 weeks reduced the risk of infection in newborns.

IVIG preparations are also used to treat sepsis, especially in combination with Antibiotics. The recommended blood level is greater than 800 mg/kg.

Following allogeneic bone marrow transplantation, for the prevention of CMV and other infections, IVIG is administered weekly for 3 months, and then 500 mg/kg every 3 weeks for 9 months. For the treatment of autoimmune diseases, IVIG dosages are 250–1000 mg/kg over 2–5 days, every 3 weeks. Children with autoimmune thrombocytopenic purpura are administered 400 mg/kg for 2 days, and adults receive 1 g/kg over 2 or 5 days.

Normal human immunoglobulin for intramuscular administration. These preparations are manufactured from a pool of over 1000 donor blood plasmas, thereby containing a wide spectrum of antibodies of various specificities that reflect the collective immunity status of the donor cohort, directed against all types of infections previously contracted by Donors or developed As a result of vaccination. They are prescribed for the prevention of infectious diseases such as hepatitis, measles, pertussis, meningococcal infection, poliomyelitis, and influenza, as they contain small amounts of antibodies against these infectious agents. However, they are poorly suited for the replacement therapy of antibody deficiency syndromes in Primary and secondary immunodeficiencies. A large portion of the immunoglobulin is degraded at the injection site, which at best may induce beneficial immunostimulation. Normal human immunoglobulin for intramuscular administration is available in 1.5 mL ampoules. The preparation is administered intramuscularly.

Measles prevention. Starting from 3 months of age, for unvaccinated individuals who have not had measles, no later than 4 days after contact with an infected person: for children — 1.5 or 3 mL (depending on health status and time elapsed since contact); for adults — 3 mL as a single dose. Poliomyelitis prevention. For unvaccinated children or those who have not completed the full vaccination course, as early as possible after contact with a patient presenting the paralytic form of poliomyelitis — 3–6 mL as a single dose. Hepatitis A prevention. For children aged 1–6 years — 0.75 mL; aged 7–10 years — 1.5 mL; over 10 years and adults — 3 mL as a single dose; a repeated dose may be administered based on indications no earlier than 2 months later. Influenza prevention and treatment. For children under 2 years — 1.5 mL; aged 2–7 years — 3 mL; over 7 years and adults — 4.5–6 mL as a single dose. In severe forms of influenza, repeated administration is indicated after 24–48 hours. Pertussis prevention. For children who have not had pertussis — 3 mL twice with an interval of 24 hours. Meningococcal infection prevention. For children from 6 months to 7 years of age, no later than 7 days after contact with a patient suffering from a generalized form of infection (regardless of the pathogen's serogroup) — 1 mL (up to 3 years of age inclusive) or 3 mL (over 3 years of age).

Hyperimmune immunoglobulins

Targeted hyperimmune immunoglobulins are derived from the blood serum of specially immunized donors. These preparations contain high titers of antibodies against specific pathogens and are used for emergency immunotherapy and immunoprophylaxis of tetanus, influenza, tick-borne encephalitis, and staphylococcal infection.

Human antistaphylococcal immunoglobulin is used for the treatment of staphylococcal-Etiology diseases in children and adults. In generalized staphylococcal infection, the immunoglobulin is administered intramuscularly once daily. The minimum single dose is 5 IU of anti-alpha-staphylolysin per 1 kg of body weight (for children under 5 years, the single dose is no less than 100 IU). In localized staphylococcal infection, the minimum single dose of the preparation is no less than 100 IU. The course of treatment consists of 3–5 injections administered daily or every other day, depending on the severity of the disease, the patient's condition, and the therapeutic effect. It is available in 3 mL ampoules (1 dose

— 100 IU) and 5 mL ampoules (1 dose — 100 IU).

Human immunoglobulin against Herpes simplex virus type 1 for intramuscular administration. It is used for the treatment of acute or acute exacerbations of chronic herpesvirus type 1 infection (herpes labialis). The immunoglobulin is administered at 4.5 mL (3 ampoules) intramuscularly once every 3 days, for up to 5 injections. It is available in 1.5 mL ampoules as a 10% solution of the immunologically active protein fraction.

Human immunoglobulin against herpes simplex virus type 2 for intramuscular administration. It is used for the treatment of acute or acute exacerbations of chronic herpesvirus type 2 infection (herpes genitalis). Primary and recurrent genital herpes infection: 1.5 mL (1 dose) intramuscularly once every three days. The course of treatment is 7 injections, along with topical treatment of herpetic vesicular rashes. Genital herpes infection in pregnant women: the first course of treatment is administered after 12 weeks of pregnancy. The preparation is administered intramuscularly at 1.5 mL (1 dose) once every three days, for a total of 6 injections. The second course is administered after 36 weeks of pregnancy. The preparation is administered intramuscularly at 1.5 mL (1 dose) once every three days, for 6 injections. The preparation is also used as local instillations into the Urethra and Vagina. The immunoglobulin is administered intravaginally using a needleless syringe for 5 days following prior vaginal washing with normal saline. It is available in 1.5 mL ampoules.

Zostevir (liquid human varicella-zoster virus immunoglobulin) for intramuscular administration. It is used for the treatment of acute or acute exacerbations of chronic herpesvirus type 3 infection (herpes zoster), as well as in debilitated patients with immunodeficiencies, following immunosuppression or bone marrow transplantation. The immunoglobulin is administered at 3 mL (2 ampoules) intramuscularly once every 3 days for up to 9 injections. It is available in 1.5 mL ampoules.

Herpimmun 6 (liquid human herpesvirus type 6 immunoglobulin) for intramuscular administration. It is used for the treatment of patients with herpetic infections involving The Nervous system caused by herpesvirus type 6. It is administered intramuscularly at 3 mL (two 1.5 mL ampoules) once every three days for up to 9 injections. It is available in 1.5 mL ampoules.

Human anticytomegalovirus immunoglobulin for intramuscular administration. It is used for the treatment of cytomegalovirus infection in adults and children. It is administered intramuscularly once daily. For the treatment of CMV infection in newborns, it is administered at 0.5 mL per 1 kg of body weight per day with an interval of 2–3 days. The course of treatment is up to 3 injections. For the treatment of CMV infection in young children, it is administered at 1.5 mL (1 ampoule) with an interval of 5 days between injections. The course of treatment is up to 5 injections. For women with a complicated obstetric history, including pregnant women, 1.5 mL (1 ampoule) is given once every 3 days. The course of treatment is up to 5 injections. For Central Nervous System involvement in adults, 4.5 mL (three 1.5 mL ampoules) is administered once every 3 days. The course of treatment is up to 5 injections. It is available in 1.5 mL ampoules.

Cytotect (liquid human anticytomegalovirus immunoglobulin) for intravenous administration is used: for acute CMV infection in premature newborns and infants; based on indications in children with primary and secondary immunodeficiencies; for the treatment of CMV infection in recipients following bone marrow or Organ and tissue transplantation. It is administered as an intravenous drip (1 mL/min). As a single dose, 50 IU/kg of body weight. For transplantation, administration (1 mL/kg of body weight) should begin on the day prior to transplantation and on the day of transplantation. For the treatment of manifest infection, 2 mL/kg is given every two days until clinical symptoms disappear. It is available in 10% 10 mL and 5% 50 mL vials.

Human immunoglobulin against Epstein-Barr virus. It is used for the treatment of diseases caused by Epstein-Barr virus (EBV), including encephalitis, encephalomyelitis, meningoencephalitis, arachnoencephalitis, arachnoiditis, encephalopolyradiculitis, and infectious mononucleosis. In adults, the immunoglobulin is administered intramuscularly at 4.5 mL (three 1.5 mL ampoules) once every three days. The course of treatment is up to 5 injections. For the treatment of infectious mononucleosis of EBV etiology in children over 3 years of age, the immunoglobulin is administered intramuscularly at 3 mL (two 1.5 mL ampoules) once every three days. The course of treatment is up to 5 injections. It is available in 1.5 mL ampoules.

Hepatoimmun (liquid human hepatitis B virus immunoglobulin). Emergency prophylaxis of hepatitis B: following contact with infectious material (blood, plasma, serum), after needlestick injuries, and when infectious material comes into contact with mucous membranes (mouth, eyes, etc.). For the purpose of emergency hepatitis B prophylaxis, the preparation is administered intramuscularly at a dose of 6–10 IU of the preparation per 1 kg of body weight as early as possible after contact (within 24–48 hours). Emergency prophylaxis in adults and children over 10 years belonging to high-risk groups for hepatitis B virus infection (contacts of hepatitis B sources, prior to surgeries, blood transfusions, hemodialysis, etc.) who are unvaccinated against hepatitis B: the preparation is administered at 6–8 IU per 1 kg of body weight. For children under 10 years, the preparation is administered at a dose of 100 IU. It is available in 1 mL ampoules (1 mL — 50 IU).

Human antichlamydial immunoglobulin is used for the Treatment of Chlamydial infection (involving the urogenital tract — salpingitis, salpingo-oophoritis, colpitis, urethritis, prostatitis, cystitis, urethroprostatitis, pregnancy loss, Infertility, etc.). For the treatment of urogenital Chlamydial infection in adults, including pregnant women, the immunoglobulin is administered at 1.5 mL (1 dose) once every 3 days intramuscularly, for up to 6 injections. The preparation is also used as local instillations into the urethra and vagina at a dose of 1.5 mL (1 ampoule). It is available in 1.5 mL ampoules (1 dose).

Ureaplasma-immun (liquid human Ureaplasma urealyticum immunoglobulin) is used for the treatment of ureaplasmosis. The preparation is administered intramuscularly at 3 mL (two 1.5 mL ampoules) once every three days, for up to 7 injections. It is available in 1.5 mL ampoules (1 dose).

Mycoplasma-Immune (Liquid human immunoglobulin against p120 Mycoplasma hominis) is used to treat mycoplasmosis. The drug is administered intramuscularly at a dose of 3 ml (two 1.5 ml ampoules) once every three days, for up to 7 injections. It is available in 1.5 ml ampoules (1 dose).

Human immunoglobulin against Toxoplasma gondii is used for the treatment of toxoplasmosis (urogenital tract infections, in women with a complicated obstetric history, including pregnant women). The first course of treatment for pregnant women presenting with symptoms of toxoplasma infection or chronic toxoplasmosis and associated obstetric pathology is carried out after 12–15 weeks of gestation. The immunoglobulin is administered intramuscularly at 1.5 ml once every 3 days for a course of 7–10 injections. The second course of treatment is performed after 30 weeks of gestation following the same schedule. The first course of treatment for patients with symptoms of urogenital tract involvement against the background of toxoplasmosis is conducted according to the same regimen. Women are prescribed a second course of immunoglobulin therapy 4 weeks after the first one, under medical supervision. It is available in 1.5 ml ampoules (1 dose).

Anti-Rh0(D) human immunoglobulin suppresses the synthesis of antibodies against a rhesus-positive fetus in a rhesus-negative woman via a feedback mechanism. Anti-Rh0(D) human immunoglobulin is administered to Rh0(D)-negative women who are not sensitized by the Rh0(D) antigen—that is, those who have not produced rhesus antibodies after giving birth to an Rh0(D)-positive child, as well as in cases of artificial termination of pregnancy in women not sensitized to the Rh0(D) antigen when the father is Rh0(D)-positive. The immunoglobulin is administered intramuscularly as a single dose of 7 ml. For postpartum women, it is given within the first 48 hours after delivery. In cases of artificial termination of pregnancy, it is administered immediately after the procedure under medical supervision. It is available in 7 ml vials (1 dose).

Novikov D.K. and Novikova V.I. (2004) developed a method for predicting the efficacy of immunoglobulin preparations. It was found that the therapeutic effect of immunoglobulin drugs depends on the presence of Fc receptors on the patients' leukocytes. The method consists in determining the number of leukocytes carrying receptors for the Fc fragments of immunoglobulins in the patients' blood prior to treatment, as well as the ability of leukocytes to become sensitized by antistaphylococcal immunopreparations. The efficacy of immunotherapy is predicted if there are 8% or more lymphocytes and 10% or more granulocytes exceeding 100 cells per 1 µl of blood bearing Fc receptors, coupled with a positive sensitization transfer test.

The results regarding The Effect of the immunopreparation on lymphocyte sensitization are evaluated using the leukocyte migration inhibition assay, employing antigens corresponding to the antibodies present in the antiserum, such as staphylococcal antigens. If staphylococcal antigens inhibit the migration of leukocytes treated with antistaphylococcal plasma, but do not inhibit the migration of leukocytes treated with normal plasma, the reaction is considered positive.

The proposed method makes it possible to predict the efficacy of both specific (using immune preparations) and non-specific (via Fc receptors) immunoglobulin immunotherapy.

Monoclonal Antibody-Based Drugs

These drugs are derived from antibody-producing hybrid animal and human cells. Their primary clinical application is to suppress pathogens or modify the immune response by binding certain key pathogenic factors with Monoclonal Antibodies. Examples include antibodies developed against respiratory syncytial virus; TNF-α to suppress inflammation in sepsis; and CD20+ lymphocytes for the treatment of rheumatoid arthritis and systemic lupus erythematosus. Below are some common APPLICATIONS OF MONOCLONAL antibodies:

- TNF-α antibodies — adalimumab (Humira) is administered subcutaneously into the abdomen or anterior thigh at a dose of 40 mg/0.8 ml once every 2 weeks.

- Antibodies against CD20 B-lymphocytes for immunosuppression — rituximab (MabThera) is prescribed at 500 mg once a week via intravenous infusion.

- Antibodies against activated lymphocytes — leflunomide (Lefno, Arava) blocks pyrimidine synthesis and is prescribed at 100 mg once daily for 3 days, followed by 20 mg once daily.

- Antibodies against interleukin-1 receptors — anakinra (Kineret) is administered orally at 100 mg once daily; tocilizumab (Actemra), an antibody against the IL-6 receptor, is administered intravenously at a dose of 8 mg/kg once a week (Phase III clinical trials have been completed and a Biologics License Application has been submitted to the FDA) for the treatment of rheumatoid arthritis;

- anti-IgE antibodies for severe allergic reactions (Xolair).

Bone marrow, leukocyte, and Spleen preparations

Myelopid is derived from a culture of porcine bone marrow cells. It contains bone marrow-derived immunomodulators known as myelopeptides. Myelopid stimulates anti-tumor immunity, phagocytosis, antibody-producing cells, and the proliferation of granulocytes and macrophages in the bone marrow. It is used in the treatment of septic, protracted, and chronic bacterial infections, as well as secondary immunodeficiencies, due to its ability to enhance antibody synthesis in the presence of antigens. Myelopid (5 mg vial) is administered intramuscularly, daily or every other day. The single dose is 0.04-0.06 mg/kg. The course of therapy consists of 3-10 injections administered every other day.

Leukocyte transfer factor ("transfer factor") is a group of BIOLOGICALLY ACTIVE SUBSTANCES extracted from the leukocytes of healthy or immunized donors through multiple consecutive freeze-thaw cycles. Transfer factors enhance delayed-type hypersensitivity to specific antigens. The drug prevents The Development of immunological tolerance, enhances T-cell differentiation, neutrophil chemotaxis, interferon production, and immunoglobulin synthesis (primarily Class M). The single dose for adults is 1-3 units of dry substance. It is used in the treatment of primary immunodeficiencies, particularly of the macrophage type, and secondary immunodeficiencies of the lymphoid type (associated with defects in T-cell differentiation and proliferation, impaired chemotaxis, and antigen presentation).

Cytokines are a group of biologically active glycopeptide mediators secreted by immunocompetent cells, as well as fibroblasts, endothelial, and epithelial cells. The main areas of cytokine therapy include:

- suppression of inflammatory cytokine production (IL-1, TNF-α) using anti-inflammatory agents and monoclonal antibodies;

- correction of immunoreactivity deficiencies using cytokines (IL-2, IL-1 preparations, interferons);

- enhancement of the immunostimulatory effect of vaccines using cytokines;

- stimulation of anti-tumor immunity using cytokines.

Betaleukin is recombinant IL-1β, available in ampoules of 0.001;

0.005 or 0.0005 mg (5 ampoules). It stimulates leukopoiesis in leukopenia caused by cytostatics and irradiation, as well as the differentiation of immunocompetent cells. It is used in oncology, for postoperative complications, and protracted purulent-septic infections. It is administered as an intravenous drip at a dose of 5 ng/kg for immunostimulation; 15-20 ng/kg for leukopoiesis stimulation daily in 500 ml of 0.9% sodium chloride solution over 1-2 hours. The course consists of 5 infusions.

Roncoleukin is recombinant IL-2. It stimulates T-lymphocyte proliferation and activates them, transforming them into cytotoxic and killer cells with an expanded lytic capacity, enabling them to destroy pathogenic microorganisms and malignant cells. It enhances immunoglobulin production by B-lymphocytes and activates the function of monocytes and tissue macrophages. Indications include signs of immunodeficiency, purulent-inflammatory diseases, sepsis, peritonitis, abscesses and Phlegmon, Pyoderma, tuberculosis, hepatitis, AIDS, and oncological diseases. For sepsis, it is administered at 0.25-1 mg (25 thousand - 1 million IU) in 200-400 ml of 0.9% sodium chloride solution as an intravenous drip at a rate of 1-2 ml/min for 4-6 hours; for oncological diseases, 1-2 million IU 2-5 times at intervals of 1-3 days; 25,000 IU in 5 ml of saline is administered for sinusitis into the maxillary or frontal sinuses; urethral instillations for chlamydia at 50 thousand IU daily (14-20 days); orally for yersiniosis and diarrhea at 500 thousand - 2,500,000 IU in 15-30 ml of distilled water on an empty stomach daily for 2-3 days. Ampoules contain 0.25 mg (250 thousand IU), 0.5 mg (500 thousand IU), and 1 mg (1 million IU).

Neupogen (filgrastim), a recombinant granulocyte colony-stimulating factor (G-CSF), stimulates the production of functionally active neutrophils and, partially, monocytes within the first 24 hours after administration, and activates hematopoiesis (for harvesting autologous blood and bone marrow for transplantation). It is used for neutropenia, including chemotherapy-induced neutropenia, at a dose of 60 million IU (2 ml, 10 mcg/kg/day) subcutaneously once daily. If the neutrophil count exceeds 1x109/l for 3 consecutive days, the dose is reduced to 30 million IU (1 ml, 5 mcg/kg/day) subcutaneously. The drug is discontinued after the neutrophil count remains above 1x109/l for an additional 3 days. For infection prevention, it is administered at a dose of 30 million IU (1 ml, 5 mcg/kg/day) subcutaneously or intravenously 24 hours after a treatment cycle for 10-14 days. For congenital neutropenia, 12 mcg/kg per day is administered subcutaneously daily.

Leukomax (molgramostim) is a recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). It is indicated for leukopenia at a dosage of 10 mcg/kg/day administered subcutaneously.

Granocyte (lenograstim) is a granulocyte colony-stimulating factor that stimulates the proliferation of granulocyte and neutrophil precursors. It is used for neutropenia at a dosage of 10 mcg/kg/day for 6 days.

Leukinferon is a complex of first-phase immune response cytokines, including IFN-α, IL-1, IL-6, IL-12, TNF-α, and MIF. For bacterial infections, the treatment course must be intensive (1 ampoule intramuscularly every other day) and transitioned to maintenance therapy only after immune recovery (1 ampoule intramuscularly twice a week).

Interferons

The Mechanism of the immunomodulatory action of interferons is mediated by enhanced receptor expression on cell membranes and the promotion of cellular differentiation. They activate natural killer cells, macrophages, and granulocytes, and suppress tumor cells. The effects of different interferons vary. Type I interferons—α and β—stimulate the expression of class I MHC molecules on cells and activate macrophages and fibroblasts. Type II interferon-gamma enhances macrophage functions, class II MHC expression, as well as the cytotoxicity of NK and T killer cells. The Biological Significance of interferons is not limited to their pronounced antiviral effect; they also exhibit antibacterial and immunomodulatory activity.

The Classification of interferons based on their origin is presented in Table 83.

Table 83. Classification of Interferons

The interferon status of an immunocompetent individual in a normal state is characterized by trace concentrations of interferons in the blood (< 4 IU/ml) and on mucous membranes; however, leukocytes from healthy individuals demonstrate a marked ability to synthesize interferons upon antigenic stimulation. In chronic viral diseases (such as herpes and hepatitis), patients show a reduced capacity to produce interferons, indicating an interferon deficiency syndrome. At the same time, interferon function in leukocytes remains preserved in children with primary lymphoid-type immunodeficiencies. Upon antigenic stimulation, all types of interferons are normally produced, although the titer of α-interferon is of primary importance for the local antiviral immune status.

Interferons at doses up to 2 million IU exert an immunostimulatory effect, whereas high doses (10 million IU) induce immunosuppression.

It should be remembered that all interferon preparations can cause fever, flu-like syndrome, neutropenia, thrombocytopenia, alopecia, dermatitis, liver and kidney dysfunction, and A number of other complications.

Leukocytic α-interferon (Egiferon, Wellferon) is used as a prophylactic agent via topical application to the mucous membrane during epidemic periods and in the treatment of early-stage acute respiratory and other viral infections. For viral rhinitis, the intranasal administration of a sufficiently high dose (3x106 IU) 3 times daily is required during the Cytology/cytology/16.html">Early stages of the disease. The drug is rapidly cleared by mucus and inactivated by its enzymes. Using it for more than a week may lead to increased inflammation. Interferon eye drops are used for viral eye infections.

Interferon-β (Betaferon) is used to treat multiple sclerosis; it inhibits viral Replication in Brain tissue and activates immune response suppressors.

Human immune γ-interferon (Gammaferon, Ingaron) exhibits cytotoxic effects, modulates T-lymphocyte activity, and activates B cells. Concurrently, the drug may suppress antibody production and phagocytosis and modify the lymphocyte response. The effect of γ-interferon on T cells persists for 4 weeks. It is used in psoriasis, HIV infection, atopic dermatitis, and malignancies.

Doses of interferon preparations for parenteral administration are selected individually: ranging from several thousand units per 1 kg of body weight to several million units per injection. The treatment course consists of 3–10 injections. Adverse reactions include flu-like syndrome. Interferon gamma is available in vials of 100 thousand IU, 500 thousand IU, 1 million IU, and 2 million IU.

Recombinant interferon alfa-2b (Intron A) is prescribed for the following conditions:

multiple myeloma - subcutaneously 3 times a week, starting at a dose of 2 x 105 IU/m2.

Kaposi's Sarcoma - 50 x 105 IU/m2 subcutaneously daily for 5 days, followed by a 9-day break, after which the course is repeated;

malignant melanoma - 10 x 106 IU subcutaneously 3 times a week every other day, for at least 2 months;

hairy cell leukemia - subcutaneously at 2 x 106 IU/m2 3 times a week for 1–2 months;

papillomatosis, Viral Hepatitis - initial dose of 3 x 106 IU/m2 3 times a week for 6 months following the surgical removal of Papillomas, and 3–4 months for hepatitis.

Laferon (Laferobion) recombinant α-2b interferon is used in the treatment of adults and children for: acute and chronic viral hepatitis; acute viral and viral-bacterial diseases, rhino- and coronavirus infections, parainfluenza infections, ARVI; meningoencephalitis; herpetic infections, including herpes zoster, skin and genital lesions, and keratitis; acute and chronic septic conditions (sepsis, septicemia, Osteomyelitis, destructive Pneumonia, purulent mediastinitis); multiple sclerosis (injections for at least one year); cancers of the kidney, breast, Ovary, and bladder, as well as melanoma (including disseminated forms); hemoblastoses such as hairy cell leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, lymphoblastic lymphosarcoma, T-cell lymphoma, multiple myeloma, and Kaposi's sarcoma; as an agent to alleviate intoxication during radiation and chemotherapy in cancer patients.

Laferon is available in strengths of: 100 thousand IU, 1 million IU, 3 million IU, 5 million IU, 6 million IU, 9 million IU, and 18 million IU.

It is prescribed for: herpes zoster—infiltrated along the nerve path near the rash at 2–3 million IU in 5 ml of saline, with Laferon mixed with LA-KOS cosmetic emulsion (or baby cream) at a ratio of 1 million IU of Laferon per 1–2 cm3 of cream applied to the papules; acute viral hepatitis B—intramuscularly at 1–2 million IU twice daily for 10 days; chronic viral hepatitis B—intramuscularly at 5 million IU, 3 times a week for 4–6 weeks (in case of a hyperthermic reaction, 0.5 g of paracetamol should be taken 20–30 minutes before Laferon administration, and antipyretics repeated 2–3 hours after the Laferon injection if necessary); chronic viral hepatitis C—intramuscularly at a dose of 3 million IU 3 times a week for 6 months; ARVI and influenza—intramuscularly at 1–2 million IU 1–2 times daily combined with intranasal administration (dilute 1 million IU in 5 ml of saline, instill 0.4–0.5 ml into each nasal passage 3–6 times daily, with the solution warmed to 30–35 °C); post-influenza meningoencephalitis—intravenous administration of 2–3 million IU twice daily (under antipyretic coverage); sepsis—intramuscularly (by drip infusion in saline) at a dose of 5 million IU for 5 days or more; cervical epithelial Dysplasia, viral and herpetically induced papillomas, and chlamydia—intramuscularly at 3 million IU for 10 days, and topically by mixing 1 million IU of Laferon with 3–5 cm³ of LA-KOS cosmetic emulsion (or baby cream) and applying it daily to the cervix using an applicator (preferably before bedtime); keratitis, keratoconjunctivitis, and keratouveitis—parabulbar administration of 0.25–0.5 million IU for 3–10 days and Laferon instillation of 250–500 thousand IU per 1 ml of saline 8–10 times daily; warts—intramuscularly at 1 million IU for 30 days; multiple sclerosis—intramuscularly at 1 million IU 2–3 times daily for 10 days, followed by 1 million IU 2–3 times a week for 6 months; cancers of various localizations—intramuscularly at 3 million IU for 5 days prior to surgery, followed by courses of 3 million IU for 10 days every 1.5–2 months; primary localized melanoblastoma—endolymphatic administration of 6 million IU/m² combined with cytostatics, with maintenance therapy consisting of weekly courses of 2 million IU/m² Laferon every other day, 4 times (course total of 8 million IU/m²) monthly; multiple myeloma—intramuscularly daily at a dose of 7 million IU/m² for 10 days (course total of 70 million IU/m2) following a course of chemo- and gamma-therapy, with maintenance therapy consisting of weekly courses at a dose of 2 million IU/m² intramuscularly, 4 injections every other day, for 6 months, with a 4-week interval between courses; Kaposi's sarcoma—intramuscularly at 3 million IU/m² for 10 days following cytostatic therapy, with maintenance therapy in weekly subcutaneous courses of 2 million IU/m², 4 times every other day, for 6 courses with a 4-week interval; basal cell carcinoma—subcutaneous injection into the tumor site of 3 million IU in 1–2 ml of water for injection for 10 days, with a repeated course after 5–6 weeks.

Roferon-A (recombinant interferon alfa-2a) is administered intramuscularly (up to 36 million IU) or subcutaneously (up to 18 million IU). For hairy cell leukemia: 3 million IU/day intramuscularly for 16–24 weeks; for multiple myeloma: 3 million IU 3 times a week intramuscularly; for Kaposi's sarcoma and renal cell carcinoma: 18–36 million IU daily; for viral hepatitis B: 4.5 million IU intramuscularly 3 times a week for 6 months.

Viferon, a recombinant interferon alfa-2b, is administered in suppositories (150,000 IU, 500,000 IU, and 1 million IU) and as an ointment (40,000 IU per 1 g). It is prescribed for infectious and inflammatory diseases (such as ARVI, pneumonia, meningitis, and sepsis), hepatitis, and skin and mucous membrane herpes. It is used as suppositories once daily or every other day; for herpes, the affected skin areas are additionally treated with the ointment 2–3 times a day. For children, suppositories of 150,000 IU are given 1 x 3 times every 8 hours for 5 days. For hepatitis, the dose is 500,000 IU.

Reaferon (interal), a recombinant interferon alpha-2, is prescribed for hepatitis B and viral meningoencephalitis intramuscularly at 1–2x10⁶ IU twice daily for 5–10 days, followed by a dose reduction. For influenza and measles, it can be administered intranasally; for genital herpes, as an ointment (0.5x10⁶ IU/g); and for shingles, intramuscularly at 1x10⁶ IU daily for 3–10 days. It is also used in tumor treatment.

Pegylated interferon (peg-IFN), unlike conventional (short-lived) interferons, maintains its concentration in The Human Body significantly longer, meaning it exhibits prolonged activity. There are two types of peg-IFNs: peginterferon alfa-2a and peginterferon alfa-2b. These drugs form the "gold standard" for hepatitis C treatment as part of Antiviral Therapy combined with ribavirin.

The prefix peg- in the name "pegylated interferon" (an abbreviation for the chemical substance bis-monomethoxypolyethylene glycol) indicates that pegylated interferon is an interferon with an attached bis-monomethoxypolyethylene glycol molecule. Bis-monomethoxypolyethylene glycol itself has practically no effect on the course of hepatitis C, but it acts as a companion to interferon, extending its duration of action. Thus, the standout feature of pegylated interferon is its prolonged effect, allowing patients to receive injections once a week rather than three times a week as with non-pegylated Interferon Therapy. Because peginterferon stays in the body longer and its action is enhanced by polyethylene glycol, better clinical outcomes can be expected without an increase in side effects.

Pegylated interferons, both as monotherapy and in combination with ribavirin, achieve a sustained virological response (SVR) of up to 60% (in patients with genotype 1) and up to 85% in patients with hepatitis C genotypes 2 and 3. For patients with virus genotype 1, a third component—a protease inhibitor—is added to this regimen to improve efficacy and shorten treatment duration.

Pegasys ® is pegylated interferon alfa-2a (pegylated interferon alpha 2a - Pegasys). Pegasys ® is prescribed at a fixed dose of 180 mcg, regardless of body weight. If serious adverse reactions occur, the dose may be modified to 135 mcg, or in special cases to 90 mcg or 45 mcg. The ribavirin dose is 1,000 mg/day for patients weighing less than 75 kg and 1,200 mg/day for those weighing more than 75 kg (for genotypes 1 and 4), and 800 mg (regardless of body weight) for genotypes 2 and 3. The daily dose of ribavirin is divided into two intakes, and the duration of therapy is the same as that of peg-interferon.

PegIntron ® is pegylated interferon alfa-2b (pegylated interferon alpha 2b - Peg-Intron). PegIntron ® is prescribed at a dosage of 1.5 mcg per 1 kg of body weight per week. The ribavirin dose is calculated based on body weight: less than 65 kg – 800 mg/day, 65–85 kg – 1,000 mg/day, 86–105 kg – 1,200 mg/day, and more than 105 kg – 1,400 mg/day.

Currently, adding a third component—a protease inhibitor—to standard antiviral therapy with interferons and ribavirin is planned, as it significantly enhances efficacy and reduces treatment duration. The most promising protease inhibitors are telaprevir and boceprevir. For instance, studies on telaprevir have shown that adding it for 12 weeks to the standard treatment regimen in patients with viral genotype 1 substantially increases the SVR rate. Furthermore, telaprevir is expected to help shorten treatment duration for genotype 1 patients from 48 to 24 weeks. In other studies, more than half of the patients who failed to clear the virus using only two drugs were cured by adding boceprevir to their regimen. Among patients who experienced a relapse, retreatment with three drugs was successful in 75% of cases, compared to 29% for those receiving only two drugs. The Use of telaprevir and boceprevir in the EU and the US was scheduled to begin in 2012.

Another promising direction in hepatitis C treatment is the development of polymerase inhibitors. One study demonstrated that adding the inhibitor R7128 to standard therapy in non-responders resulted in SVR achievement in the majority of patients. Clinical trials are currently underway evaluating the combined use of a polymerase inhibitor and a protease inhibitor in patients with chronic hepatitis C.

The duration of therapy for chronic viral hepatitis C ranges from 16 to 72 weeks. The optimal treatment length depends on the hepatitis C virus genotype: it is 48 weeks for infections with genotypes 1 and 4, and 24 weeks for genotypes 2 and 3.

Treatment duration can be shortened from 24 to 16 weeks for genotypes 2 and 3, or from 48 to 24 weeks for genotypes 1 and 4, in patients who achieve a rapid virological response at week 4, provided they have a low baseline viral load and no significant liver fibrosis. Conversely, the duration of therapy can be extended up to 72 weeks depending on interim treatment results (in patients with a partial early virological response—defined as a reduction in HCV RNA levels by 2 or more decimal logs by week 12 of treatment, HIV co-infection, and advanced liver fibrosis). Modifying treatment timelines and drug dosages based on interim results is referred to as "response-guided therapy" or virological response-guided therapy. Response-guided therapy allows treatment to be individualized for each specific patient, determining therapy duration based on the patient's baseline viral load and virological response during treatment.

During antiretroviral therapy, it is necessary to regularly monitor blood leukocyte levels and determine the absolute neutrophil count. Platelet and Hemoglobin levels should also be checked via a complete blood count. Reaching critical thresholds requires dose modification or discontinuation of the drugs. Recommendations for interferon dose adjustment are presented in Table 84.

Table 84. Recommendations for interferon dose adjustment

Note: * if the dose is maintained outside of manufacturer recommendations, the absolute neutrophil count must be determined more frequently, and patients should be counseled on the consequences of neutropenia. In patients with liver cirrhosis, post-liver transplantation, or HIV/HCV co-infection who maintain neutropenia despite dose reduction, granulocyte colony-stimulating factor must be administered.

** If the dose is maintained outside of manufacturer recommendations, the platelet count must be monitored more frequently, and patients should be carefully observed for bleeding symptoms or hematomas.

Biostimulants of various origins

Many signals connecting the central nervous system and the immune system are mediated by biologically active substances that function as Neurotransmitters and neuromodulators in the CNS, and as hormones in peripheral tissues. These include hormones, biogenic amines, and peptides. Neuroregulatory biological MEDIATORS AND HORMONES influence lymphocyte differentiation and functional activity. For instance, the adenohypophysis secretes immunotropic mediators such as somatotropin, adrenocorticotropic hormone, gonadotropic hormones, a group of thyrotropic hormones, as well as a specialized hormone—thymocyte growth factor.

Heparin is a mucopolysaccharide that stimulates hematopoiesis, enhances the release of leukocytes from the bone marrow reserve, increases the functional activity of cells, promotes lymphocyte proliferation in Lymph Nodes, and raises the resistance of peripheral blood erythrocytes to hemolysis. At doses of 5,000–10,000 IU, it exhibits fibrinolytic, antiplatelet, and mild immunosuppressive effects, and enhances the action of Steroids and cytostatics. Administered intradermally at multiple points in small doses ranging from 200 to 500 IU, it exerts an immunoregulatory effect—normalizing decreased lymphocyte counts and their subpopulation profile—while exerting a stimulatory effect on neutrophils.

Vitamins

Vitamins alter the activity of biochemical processes within cells, including immunological ones. Certain forms of immunological deficiency are associated with a deficit of specific vitamins. An example is the primary form of phagocytic defect—Chediak-Higashi syndrome. In this condition, administration of Vitamin C at a dose of 1 g daily for several weeks activates the enzymatic oxidation-reduction systems of phagocytes (neutrophils and macrophages) to the stage of compensating their bactericidal function.

Ascorbic acid normalizes the activity of T-lymphocytes and neutrophils in patients with initially low baseline parameters. However, high doses (10 g) induce immunosuppression.

Vitamin E (tocopheryl acetate, α-tocopherol) is found in sunflower, corn, soybean, and sea buckthorn oils, as well as in eggs, milk, and meat. It possesses antioxidant and immunostimulatory properties and is used in cases of muscular dystrophy, sexual dysfunction, and during chemotherapy. It is prescribed orally and intramuscularly at 0.05–0.1 g daily for 1–2 months. Administering vitamin E at a daily dose of 300 IU for 6–7 days orally increases the count of leukocytes, T-lymphocytes, and B-lymphocytes. In combination with selenium, vitamin E increases the number of antibody-producing cells. Vitamin E is believed to alter the activity of lipoxygenase and cyclooxygenase, enhance IL-2 production and immunity, and suppress tumor growth. Tocopherol at a daily dose of 500 mg normalizes immune status parameters.

Zinc acetate (10 mg twice daily, 5 mg for up to 1 month) acts as a stimulator of antibody production and delayed-type hypersensitivity. Zinc-thymulin is considered one of the primary thymic hormones. Zinc preparations increase resistance to respiratory infections. A deficiency of this micronutrient leads to a quantitative deficit in antibody-producing cells and defects in the Synthesis of the IgG2 and IgA subclasses. A distinct form of primary immunological deficiency has been described—"acrodermatitis enteropathica with combined immunological deficiency"—which is almost entirely corrected by zinc supplementation, such as zinc sulfate. Administration is continuous. Zinc oxide is prescribed in powder form after meals with milk or juices. For acrodermatitis, the dose is 200–400 mg daily, followed by a maintenance dose of 50 mg/day. For infants, it is 10–15 mg/day; for adolescents and adults, 15–20 mg/day. For prophylactic purposes, the dose is 0.15 mg/kg/day.

Lithium exerts an immunotropic effect. Lithium chloride at a dose of 100 mg/kg or lithium carbonate at an age-appropriate single dose produces an immunomodulating effect in immunological deficiency caused by a deficit of this micronutrient. Lithium enhances granulocytopoiesis and the production of colony-stimulating factor by bone marrow cells, which is utilized in the therapy of hypoplastic hematopoietic states, neutropenias, and lymphopenias. It also activates phagocytosis. The administration regimen involves gradually increasing the dose from 100 mg to 800 mg/day, followed by a tapering down to the initial dose.

Phytoimmunomodulators

Herbal infusions and decoctions exhibit immunomodulating (immunostimulating) activity.

Eleutherococcus does not alter immune parameters under normal immune status. It exhibits interferonogenic activity. In cases of T-cell deficiency, it normalizes parameters, enhances the functional activity of T-cells, activates phagocytosis, and stimulates non-specific immune responses. It is administered as 2 ml of liquid extract 30 minutes before meals, 3 times a day, for 3–4 weeks. For children, to prevent recurrences of acute respiratory infections (ARIs), the recommended dosage is 1 drop per year of life, 1–3 times a day for 3–4 weeks.

Ginseng enhances physical performance and the body's overall resistance to diseases and adverse factors; it causes no harmful side effects and can be used for extended periods. Ginseng ROOT is a potent stimulant of the central nervous system, yet it produces no negative side effects and does not disrupt Sleep. Ginseng preparations stimulate tissue Respiration, increase gas exchange, improve blood composition, normalize Heart rhythm, enhance visual sensitivity, accelerate healing processes, inhibit the vital activity of certain bacteria, and increase radiation resistance. These preparations are recommended for use during the autumn-winter period. The most stimulating effect is observed when using ginseng powder and a 40-proof alcohol infusion. A single dose is 15–25 drops of the alcoholic tincture (1:10) or 0.15–0.3 g of ginseng powder. Take 2–3 times a day before meals in courses of 30–40 days, followed by a break.

Chamomile flower infusion contains Essential Oils, azulene, anthemic acid, and Heteropolysaccharides, which possess immunostimulating properties. Chamomile infusion is used to boost the immune system's activity following hypothermia, during prolonged stress, and in the autumn-spring period for the prevention of colds. The infusion is taken orally, 30–50 ml 3 times a day for 5–15 days.

Echinacea (Echinacea purpurea) exerts immunostimulating and anti-inflammatory effects, activates macrophages, the secretion of cytokines and interferons, and stimulates T-cells. It is used to prevent colds in the autumn-spring period, as well as to treat viral and bacterial infections of the upper respiratory tract, urogenital tract, etc. The recommended dosage is 40 drops 3 times a day, diluted with water. Maintenance doses are 20 drops 3 times a day orally for 8 weeks.

Immunal is an infusion composed of 80% Echinacea purpurea juice and 20% ethanol. It is prescribed at 20 drops orally every 2–3 hours for acute respiratory infections and flu, followed by 3 times a day. The course of treatment lasts 1–8 weeks.

Biostimulants-adaptogens: tincture of Schisandra chinensis, decoctions and infusions of Bidens tripartita, Chelidonium majus, Calendula, Viola tricolor, licorice root, and dandelion possess an immunocorrecting effect. Available preparations include Glyciram, Liquiriton, pectoral elixir, and Caleflon.

Bacterioimmunotherapy

Mucosal dysbiosis plays a crucial role in pathology. Antibiotic therapy, cytostatic therapy, and Radiation therapy disrupt mucosal biocenosis—primarily in the intestine—leading to dysbiosis. Probiotic lactobacilli, bifidobacteria, and colibacilli secrete colicins that inhibit the growth of pathogenic bacteria. However, It is important not only to suppress pathogenic bacteria and Fungi, but also to address the deficiency of biologically active substances normally produced by the microflora during dysbiosis: vitamins (such as B12 and Folic acid) and lipopolysaccharides from Escherichia coli, which stimulate immune system activity, among others. As a result, dysbiosis is accompanied by immunodeficiency. Therefore, preparations of normal flora are used to restore intestinal biocenosis, which plays a vital role in stimulating immune system functions.

Gram-positive lactobacilli and bifidobacteria stimulate anti-infective and antitumor immunity, and induce tolerance during allergic reactions. They directly induce moderate cytokine release by immunocompetent cells, which consequently enhances the synthesis of secretory IgA. On the other hand, lactobacilli penetrating the mucous membrane can potentially cause infections and induce a systemic immune response; therefore, probiotic bacteria act as potent immunomodulators, particularly in an immunocompromised Organism. Live bacterial preparations should not be used simultaneously with ANTIBIOTICS AND CHEMOTHERAPEUTIC agents that suppress their growth.

Lactobacilli act as antagonists to pathogenic microbes and secrete enzymes and vitamins. It is recommended to prescribe them together with specific Bacteriophages that suppress pathogenic flora. Their use is not advisable in cases of candidiasis, as their acids promote fungal growth.

Dry Bifidumbacterin consists of freeze-dried live bifidobacteria. For adults: 5 tablets 2–3 times a day, 20 minutes before meals. The course lasts up to 1 month. For children: supplied in vials, diluted with warm boiled water (1 tablet per 1 teaspoon), at 1–2 doses 2 times a day. It is used for dysbiosis, enteropathies, artificial feeding in infants, treatment of premature infants, acute intestinal infections (dysentery, salmonellosis, etc.), chronic intestinal diseases (gastritis, duodenitis, colitis), radiation therapy and tumor chemotherapy, candidal vaginitis, food intolerances and food allergies, dermatitis, eczema, normalization of oral mucosal microflora in stomatitis and periodontitis, diabetes mellitus, chronic Diseases of the liver and Pancreas, and work under hazardous and extreme conditions.

Dry Bifikol contains live freeze-dried bifidobacteria and Escherichia coli strain M-17. For adults and children over 3 years old: 3–5 tablets 20–30 minutes before meals, 2 times a day, washed down with water. The course lasts 2–6 weeks.

Bifiform contains at least 10⁷ Bifidobacterium longum as well as 10⁷ Enterococcus faecium in capsules. For grade I–II dysbiosis: 1 capsule 3 times a day for a 10-day course; for grade II–III dysbiosis, the course is extended to 2–2.5 weeks.

Linex is a combination preparation containing three components of natural microflora from different sections of the intestine: each capsule contains 1.2×10⁷ live lyophilized bacteria—Bifidobacterium infantis, Lactobacillus acidophilus, and Enterococcus faecium—which are resistant to antibiotics and chemotherapeutic agents. It maintains microbiocenosis throughout all sections of the intestine, from the Small Intestine to the rectum. Dosage: adults take 2 capsules 3 times a day, washed down with boiled water or milk; children under 2 years old take 1 capsule 3 times a day, washed down with liquid or by mixing the capsule contents with liquid.

Dry Colibacterin is a freeze-dried live Escherichia coli strain M-17, which acts as an antagonist to pathogenic microbes, stimulates immunity, and produces enzymes and vitamins. Adults take 3–5 tablets 2 times a day, 30–40 minutes before meals, washed down with alkaline mineral water. The course lasts from 3 weeks to 1.5 months.

Bifikol is a combination preparation.

Bactisubtil contains sporobacteria of the strain IP 5832 (ATCC 14893), 35 mg containing 10⁹ spores. It is used for diarrhea and dysbiosis, 1 capsule 3–10 times a day, 1 hour before meals.

Enterol-250, unlike bacteria-containing preparations, contains Saccharomyces boulardii yeast, which acts as an antagonist against pathogenic bacteria and fungi. It is recommended for diarrhea and dysbiosis, and can be used in combination with antibacterial therapy. The dosage for children under 3 years old is 1 capsule 1–2 times a day for 5 days; for children over 3 years old and adults, it is 1 capsule 2 times a day for 7–10 days.

Hylak Forte contains metabolic products of probiotic lactobacillus strains and normal intestinal microorganisms (Escherichia coli and Enterococcus faecalis): lactic acid, Amino Acids, short-chain Fatty acids, and lactose. It is compatible with antibiotic therapy. Simultaneous use of antacid preparations is not recommended due to the potential neutralization of the lactic acid contained in Hylak Forte. It is prescribed at a dose of 20–40 drops 3 times a day for

2–3 weeks (for infants, 15–30 drops 3 times a day), taken in a small amount of liquid before or during meals, excluding milk and dairy products.

Gastrofarm contains live lyophilized cells of Lactobacillus bulgaricus 51 and their metabolic byproducts (lactic and malic acids, nucleic acids, a range of amino acids, polypeptides, Polysaccharides). Taken orally 3 times a day, chewed with a small amount of water. The single dose is 1/2 tablet for children and 1–2 tablets for adults.