[Efficacy and safety of bacterial lysate OM-85 in the treatment of uncomplicated acute respiratory infections: a double-blind, placebo-controlled, multicenter, randomized trial].

AIM: To evaluate the efficacy and safety of OM-85 in the treatment of uncomplicated acute respiratory infections (ARI) in adults. MATERIALS AND METHODS: A double-blind, placebo-controlled, multicenter, randomized trial included 556 patients (18-60 years old) with mild and moderate ARI and negative results of polymerase chain reaction analysis for SARS-CoV-2 RNA and rapid test for influenza A and B viruses. Patients were randomized into two groups: in the first group (n=278), patients received OM-85 (Broncho-munal®) one capsule 7 mg/day for 10 days, while the second group (n=278) was treated with placebo in the same regimen. The primary endpoint was the dynamics of the severity of symptoms over 3, 5, 7 and 10 days of treatment according to the 21-item Wisconsin Upper Respiratory Symptom Survey (WURSS-21), which was assessed by the area under the curve. Secondary efficacy criteria were the dynamics of the severity of symptoms according to the Common Cold Questionnaire (CCQ), the time to the resolution of symptoms according to WURSS-21 and CCQ, the proportion of patients with body temperature below 37°C on each day of treatment, frequency of the need for systemic antibacterial therapy. RESULTS: The superiority of OM-85 over placebo by primary endpoint was observed on the 5th, 7th and 10th days of treatment. OM-85 efficacy has also been proven by secondary criteria. OM-85 shortened the time until the symptoms of ARI resolved according to the WURSS-21 and CCQ, increased the proportion of patients with body temperature below 37°C by 2-9 days. The time needed to resolve the symptoms of disease in 20% of patients according to WURSS-21 was 7 and 9 days in patients taking OM-85 and placebo, respectively. Bacterial lysate increased the probability of complete disappearance of symptoms according to CCQ by 45.7% compared to placebo. The analysis of the frequency and severity of adverse events, laboratory tests, physical and instrumental examination results during treatment confirmed the good tolerability and safety of OM-85. CONCLUSION: The study confirmed the efficacy and safety of OM-85 in the complex treatment of ARI in adults.

[Application of HS221GI in treatment of influenza and ARVI in adults: a new approach - managing virus-induced inflammation. Results of a double-blind, randomized, placebo-controlled, multicenter clinical trial].

AIM: Evaluation of the efficacy and safety of the drug Aterixen® (XC221GI, 1-[2-(1-methylimidazole-4-yl)-ethyl]perhydroazine-2,6-dione), in the treatment of uncomplicated forms of influenza and other ARVI in adults. MATERIALS AND METHODS: The phase III clinical trial enrolled 260 people aged 18-65 years with mild and moderate forms of influenza or other ARVI. Patients were randomly assigned to two groups: in group 1 (n=130), patients were prescribed the drug Aterixen® in tablets of 100 mg 2 times a day for 5 days; in group 2 (n=130) - a placebo corresponding to the drug, in the same regimen. The primary endpoint of the efficacy assessment was the time in hours from the first administration of the drug to clinical improvement. The main efficacy analysis was performed in a population of patients with PCR-confirmed influenza or ARVI who completed the study according to the protocol (per protocol infected). Additionally, efficacy was evaluated in ITT and PP populations, including patients with both identified and undetected pathogen. The population for safety analysis included all patients, without exception, who were exposed to at least one exposure to the study drug or placebo. RESULTS: A statistically significant superiority of the drug Aterixen® over placebo in primary endpoint was revealed in both the main and additional analysis in all studied populations: clinical improvement in the group of the studied drug occurred 24 hours faster compared with the placebo group. The evaluation of the effectiveness of secondary endpoints confirmed the superiority of the drug Aterixen® over placebo in terms of relief of catarrhal symptoms and symptoms of intoxication. A favorable safety profile of the drug has been demonstrated. CONCLUSION: The drug has demonstrated a favorable safety profile for use in outpatient practice. Aterixen® is an effective and safe treatment for influenza and other ARVI in adults.

[New opportunities for preventive anti-inflammatory therapy in the management of patients with moderate and severe COVID-19].

The specific feature of new coronavirus infection (COVID-19) is high risk of hyperinflammatory response or cytokine storm development, which underly the pathogenesis of several life-threatening conditions and determine the disease outcomes. Pathophysiological features of COVID-19 justify the search of effective drugs capable to control the hyperinflammatory response. AIM: To evaluate the efficacy and safety of Aterixen (1-[2-(1-Мethylimidazol-4-yl)-ethyl]perhydroazin-2,6-dion) for achieving clinical improvement in adult patients hospitalized with moderate and severe COVID-19. MATERIALS AND METHODS: Multicenter, adaptive, randomized, double-blind, placebo-controlled, phase III study to evaluate the efficacy and safety of Aterixen , tablets, 100 mg, in patients with COVID-19. The study analysis included 116 patients who, by randomization, were divided into 2 groups: 57 patients were included in the Aterixen drug group and 59 patients were in the placebo group. RESULTS AND CONCLUSION: Obtained results have shown high efficacy and statistically significant superiority of Aterixen over placebo. Thus, it allows us to consider it as viable medication for COVID-19 pathogenetic therapy.

Bacterial Lysate Complex Administered Intranasally Suppresses Inflammation in an In Vivo Model of Aseptic Lymphadenitis.

The effect of a bacterial lysate complex IRS 19 on local and systemic manifestations of inflammation was studied in a rat model of aseptic lymphadenitis. Injection of λ-carrageenan into the cervical lymph node via surgical approach caused an increase in the thickness of the capsule, disturbances in histoarchitecture, the appearance of necrosis foci, histiocytosis of subcapsular and cerebral sinuses in the lymph node, as well as an increase in the level of TNFα in the blood serum and the number of circulating leukocytes and neutrophils. Course intranasal administration of bacterial lysate complex in this model dose-dependently reduced the level of these markers of the systemic inflammatory response and the severity of microstructural disorders in the affected lymph nodes. Thus, bacterial lysate complex after intranasal administration produces a systemic anti-inflammatory effect that goes beyond the respiratory tract.

[The assessment of a role of muramyl peptides in the treatment of patients with aggressive form of periodontitis]. / Izuchenie roli kompozitsii muramilpeptidov pri lechenii patsientov s agressivnoi formoi parodontita.

THE AIM OF THE STUDY: Was to determine the effect of the drug based on the composition of muramyl peptides isolated from the cell walls of gram-negative bacteria on the production of α-defensins and the detectability of Porphyromonas gingivalis in patients with an aggressive form of periodontitis. MATERIAL AND METHODS: 60 patients aged 28 to 40 years with an aggressive form of periodontitis were randomized into two equal groups, the main and control. In both groups, patients were removed dental deposits and taught the rules of oral hygiene, followed by three-fold control. In the main group, 200 micrograms of the drug based on the composition of muramyl peptides were additionally administered intramuscularly daily for 7 days. Initially and after 7, 21, 90 days, the level of human neutrophil peptides (hnp1-3) in blood serum and periodontal pockets was determined by the enzyme immunoassay, as well as the presence of P. gingivalis in periodontal pockets by polymerase chain reaction (PCR). RESULTS: In patients of the control group, the concentration of hnp1-3 in periodontal pockets and blood serum did not change significantly during the entire study. The use of PM in the main group caused an increase in the local and systemic levels of hnp1-3, which correlated with a persistent decrease in the detectability of P. gingivalis. CONCLUSION: The drug based on the composition of muramyl peptides of the cell wall of gram-negative bacteria potentiates the eradication of P. gingivalis by stimulating the production of hnp1-3 in patients with an aggressive form of periodontitis.

Effect of Tilorone on the Dynamics of Viral Load and the Levels of Interferons and Interleukin-1ß in the Lung Tissue and Blood Serum of Mice with Experimental Influenza.

We studied the effect of tilorone on the dynamics of IFNα, IFNγ, and IL-1ß levels in the lung tissue and blood serum in relation to viral load in the lungs of BALB/c mice with pneumonia caused by influenza virus A/Aichi/2/68 (H3N2). Tilorone was administered per os in doses of 40, 150, and 540 µg per mouse 6, 30, and 78 h postinfection, which simulated the drug regimen used in the clinic for the treatment of influenza and acute respiratory viral infections in Russia and post-Soviet countries. Tilorone reduced viral load with the maximum amplitude (2-3 lg) after 1-2 administrations. The results of studying the dynamics of the cytokine levels in the infected animals in general support the previous hypothesis that, in repeated dosing, tilorone enhances the IFN response (compensates for its deficiency) at the early stages of acute respiratory viral infections and suppresses (damps) excessive production of IFN and proinflammatory cytokines at the later stages.

[Antibacterial effect of a non-specific immunomodulator based on muramilpeptides in chronic periodontitis]. / Antibakterial'nyi effekt immunomodulyatora na osnove kompozitsii muramilpeptidov pri khronicheskom generalizovannom parodontite.

THE AIM OF THE STUDY: Was to investigate the efficacy of immunomodulatory drug based on muramilpeptides for treatment of chronic generalized periodontitis. MATERIALS AND METHODS: The study group comprised 20 patients aged 25 to 64 with severe chronic periodontal disease. Periodontal pockets content was inoculated for specific microbial pathogens before and after treatment. Twenty patients receiving conventional treatment with no muramilpeptides-based agent served as controls. RESULTS: In the main group prolonged suppression of periodontal disease provoking microbiota was seen, while in controls conventional treatment was not sufficiently effective resulting in germs growth relapse at day 21. CONCLUSION: The dynamics of the microbiological landscape of periodontal pockets after treatment proves the necessity for a correction of innate immunity in inflammatory periodontal disease.

Combination of Muramylpeptides from Gram-Negative Bacteria Corrects Cyclophosphamide-Induced Disorders of Hematopoiesis and Spleen Cell Composition in Mice with B16 Melanoma.

We studied the effect of a combination of three muramylpeptides from gram-negative bacteria (Polymuramyl) on hematological parameters, morphology of the spleen, and serum cytokine level in mice with B16 melanoma treated with cyclophosphamide. Intraperitoneal administration of cyclophosphamide to tumor-bearing animals sharply reduced the number of leukocytes, especially neutrophils, in the blood and depleted the cellular composition of the spleen white pulp. Subsequent three daily intramuscular injections of Polymuramyl in doses of 70 and 860 ng/mouse for 3 days, as well as subcutaneous injection of the reference drug filgrastim (granulocytic CSF) in a dose of 12 µg/mouse partially corrected hematopoietic disorders and restored the cellular composition of the spleen. Granulocytic CSF more effectively replenished the content of mature neutrophils in the blood, while Polymuramyl restored the content of stab neutrophils. In contrast to granulocytic CSF, administration of Polymuramyl was followed by an increase in the level of granulocyte-macrophage CSF and a tendency to an increase in the serum content of IL-6, which indicates the involvement of these cytokines in the hematopoietic activity of Polymuramyl.

[BCG, muramylpeptides, trained immunity (part II): a low molecular weight alternative to multicomponent bacterial immunostimulants for prevention of respiratory infections during a pandemic].

During a pandemic, nonspecific immunoprophylaxis of SARS-CoV-2 infection and other acute respiratory infections (ARI), which can worsen the course of COVID-19, is increasingly in demand in addition to specific immunization. BCG vaccine appears to be one of the candidate immunostimulants in this regard. At the same time, other microbe-derived preparations capable of inducing a state of trained immunity deserve attention. BCG and other bacterial immunostimulatory agents containing a large number of biologically active subunits have long been considered as objects of search for promising pharmacological substances. The review analyzes the linkages between BCG, mycobacterial adjuvants, bacterial lysates, trained immunity, muramylpeptides (MPs) and NOD2 receptors in light of the choice of a low molecular weight alternative to multicomponent bacterial immunostimulants for ARI prevention during the COVID-19 pandemic. The search for key molecules by which bacteria stimulate innate and adaptive immune responses proceeds in a spiral. On different loops of this spiral, MPs have repeatedly reproduced the nonspecific effects of multicomponent bacterial adjuvants, vaccines and immunostimulants. MPs and peptidoglycans containing MPs determine the adjuvant properties of the cell walls of mycobacteria and their peptide-glycolipid fraction (wax D). MPs were able to replace Mycobacterium tuberculosis in complete Freunds adjuvant. MPs determine the NOD2-dependent ability of BCG to induce trained immunity. Probably, MPs provide NOD2-mediated long-term prophylactic action of bacterial lysates. All of the above has prompted revisiting the previously obtained evidence of the efficacy of glucosaminylmuramyl dipeptide (GMDP) as a NOD2 agonist in treatment/prevention of respiratory infections. We speculate here that MPs, in particular GMDP, at rational dosing regimens will be able to reproduce many aspects of the nonspecific effects of BCG and multicomponent bacterial immunostimulants in preventing ARI during the COVID-19 pandemic and in the post-pandemic period.

[Clinical effectiveness of an immunomodulatory drug based on a muramylpeptide composition in the treatment of patients with chronic generalized periodontitis]. / Klinicheskaya effektivnost' immunomoduliruyushchego preparata na osnove kompozitsii muramilpeptidov pri lechenii patsientov s khronicheskim generalizovannym parodontitom.

THE AIM OF THE STUDY: To assess the efficacy of an immunomodulatory drug based on a muramylpeptide composition in the treatment of patients with chronic generalized periodontitis. MATERIALS AND METHODS: The study comprised 40 patients with chronic generalized periodontitis. In controls the treatment consisted in oral hygiene instructions, professional oral hygiene procedures and root scalling while in main study group the conventional treatment protocol was combined with intramuscular injections of muramylpeptide composition. RESULTS: The study showed significant reduction of inflammatory symptoms in periodontal tissues in muramylpeptide composition group. CONCLUSION: Muramylpeptide composition increases the threshold of tissue protection against constantly present microbial accumulations in periodontal disease patients thus providing opportunity for excluding toxic antimicrobial agents and/or antibiotics (or reducing their dosages).

Proliferative Activity of Mouse Splenocytes in Physiological Pregnancy and in Models of Spontaneous and Muramylpeptide-Dependent Abortions.

Spontaneous proliferative activity of splenocytes in female CBA mice and the response of these cells to antigens of allogeneic male BALB/c and DBA/2 mice in a mixed splenocyte culture were evaluated by 3H-thymidine incorporation in different pregnancy models. ♀CBA×♂BALB/c mating was used for modeling physiological pregnancy. Spontaneous abortions were reproduced by abortion-prone ♀CBA×♂DBA/2 mating. In order to simulate immunostimulant-induced and immunostimulant-potentiated abortions, 0.83 mg/kg muramyl dipeptide ß-heptylglycoside was intraperitoneally injected to CBA females mated with BALB/c or DBA/2 males, respectively, on gestation days 5 and 7. The increase in the rate of embryo resorption in the models of spontaneous, induced, and potentiated abortions occurred against the background of an increase in the level of spontaneous proliferation of splenocytes and a decrease in their reactivity to paternal antigens on gestation day 9.

[BCG, muramylpeptides, trained immunity (part I): linkages in the light of the COVID-19 pandemic].

It has long been known that Bacillus CalmetteGurin (BCG) vaccine provides nonspecific protection against many non-mycobacterial infections, which has been discussed in the last decade through the prism of the concept of trained immunity. Within the framework of this concept, a persistent increase in resistance to various pathogens, which occurs after an infectious disease or exposure to certain microbial agents, is associated with epigenetic reprogramming of innate immune cells and their bone marrow progenitors. The COVID-19 pandemic has drawn attention of scientists and practitioners to BCG as an inducer of trained immunity. A number of epidemiological studies have suggested a negative association between the coverage of the population with BCG vaccination and the burden of SARS-CoV-2 infection. A series of independent clinical studies of the effectiveness of this vaccine in non-specific prevention of COVID-19 has been initiated in different countries. Recently, the key role of cytosolic NOD2 receptors in BCG-induced trained immunity has been proven. This actualizes the search for effective immunoactive preparations for prevention of respiratory infections in the pandemic among low molecular weight peptidoglycan fragments of the bacterial cell wall, muramylpeptides (MPs), which are known to be NOD2 agonists. The review highlights the proven and proposed linkages between BCG, MPs, NOD2 and trained immunity in the light of the COVID-19 pandemic. Analysis of the data presented indicates the prospects for preclinical and clinical studies of MPs as potential drugs for nonspecific prevention of SARS-CoV-2 infection and/or other respiratory infections in risk groups during the pandemic. First of all, attention should be paid to glucosaminylmuramyl dipeptide, approved for clinical use in Russia and a number of post-Soviet countries for the complex treatment and prevention of acute and recurrent respiratory infections.

A Combination of Muramylpeptides from Gram-Negative Bacteria Corrects Hematological and Immunological Disorders Induced by Cyclophosphamide.

We have studied the effect of a combination of three natural muramylpeptides containing a meso-diaminopimelic acid residue (polyramyl) on the subpopulations of circulating T cells, spleen morphology, and leukocyte level in the blood of C57Bl/6 mice with cyclophosphamideinduced immunosuppression. Intraperitoneal injections of cyclophosphamide in a dose of 100 mg/kg on days 1, 3, 5, and 7 of the experiment reduced leukocyte count and the relative number of CD4+ T cells in the blood, and also depleted the cellular composition of splenic white pulp on day 10. Subcutaneous injections of polyramyl in a dose of 200 µg/mouse on days 8 and 9 practically completely restored blood leukocytes count and morphology of the splenic white pulp. Moreover, administration of polyramyl induced marked tendency to increase in the relative number of CD4+ T cells and CD4/CD8 ratio in mice with cyclophosphamideinduced immunosuppression.

Clinical and interferon-modulating efficacy of a combination of rectal and topical dosage forms of interferon-α2b in acute respiratory infections.

AIM: The aim of the study was to evaluate the clinical and interferon-modulating efficacy of a combination of rectal and topical dosage forms of IFN-α2b with antioxidants in the treatment of acute respiratory infections (ARIs) in comparison with other variants of antiviral therapy. MATERIALS AND METHODS: A total of 90 servicemen aged 19.2±0.9 years with uncomplicated forms of ARI were hospitalized not later than 48 hours after the onset of the disease. Patients were randomized into 3 groups of 30 people each. In the first group, patients received rectal suppositories containing IFN-α2b (1 million IU) and antioxidants (alpha-tocopherol acetate and ascorbic acid) twice a day for 5 days. In the second group, patients received intranasally a gel formulation containing IFN-α2b (36 000 IU/1 g) and antioxidants 3 times a day in addition to the above suppositories. In the third group, patients were prescribed umifenovir (reference drug) at dose of 200 mg 4 times a day for 5 days. The dynamics of regression of clinical manifestations of ARI in different groups, changes in concentrations of IFN-α and IFN-γ in blood plasma, as well as spontaneous and induced production of these cytokines by blood cells ex vivo were evaluated. After that, the patients were observed for another 3 months to register repeated cases of hospitalization for ARI. RESULTS: Marked tendency to accelerate the regression of symptoms of intoxication and fever was observed when intranasal dosage form of IFN-α2b was administered to patients receiving the rectal form of this cytokine. The combination of rectal and topical dosage forms of IFN-α2b with antioxidants was more effective than monotherapy with the rectal suppositories in preventing repeated hospitalization for ARI. The above combination caused the most complete correction of induced production of IFN-α by blood cells ex vivo at its initial deviation from the norm. CONCLUSION: The obtained data indicate the expediency of using the combination of rectal and topical dosage forms of IFN-α2b with antioxidants for treatment of ARI.

Effect of N-acetylcysteine on mucosal immunity of respiratory tract.

The outcome of diseases accompanied or caused by mucostasis depends both on the restoration of drainage function of the airways and on the effectiveness of immune mechanisms against pathogens. N-acetylcysteine (NAC) is widely used as mucolytic and antioxidant remedy in clinical practice. In this regard, the data of the scientific literature on the direct and indirect effects of NAC on the mucosal immunity of the respiratory tract have been reviewed. NAC possesses pleiotropic immunomodulating properties, most of which contribute to the regression of clinical manifestations of acute and chronic inflammatory diseases of the respiratory tract. Biological and pharmacological effects of NAC include improvement in rheological properties of mucus, reduction of excess mucin production, restoration of mucociliary clearance and production of sIgA, suppression of excess production of IgE and IgG4, destruction of biofilms and inhibition of their formation, suppression of adhesion of pathogenic bacteria to epithelial cells, antioxidant activity, regulation of the production of pro-inflammatory and profibrotic cytokines. There was no convincing evidence that NAC is able to suppress any component of mucosal immunity. For final conclusions on this subject, further research are required.

[Lymphocyte subpopulations, levels of interferon, and expression of their receptors in patients with chronic hepatitis B and C: Correlation with the species of viruses and the degree of liver fibrosis]. / Subpopuliatsii limfotsitov, uroven' interferonov i ékspressiia ikh retseptorov u bol'nykh khronicheskimi gepatitami V i S: zavisimost' ot vida virusov i stepeni fibroza pecheni.

AIM: To determine whether there is a correlation of the composition of circulating lymphocyte subpopulations, the serum concentrations of interferon (IFN)-α, IFN-γ, and IFN-λ3, and the lymphocyte expression of types I and II IFN receptors with the species of a disease pathogen and the degree of liver fibrosis (LF) in patients with chronic hepatitis B (CHB) and in those with chronic hepatitis C (CHC). SUBJECTS AND METHODS: The investigation enrolled 44 patients with CHC, 9 patients with CHB, and 13 clinically healthy donors. The degree of LF in the patients was determined using transient elastography. The composition of peripheral blood lymphocyte subpopulations was examined; the concentrations of IFN-α, IFN-γ, and IL-28B were estimated. RESULTS: Lymphocyte counts were higher in patients with CHC and in those with CHB than those in healthy donors; and the number of neutrophils was lower. There were no differences between the groups in the composition of lymphocyte subpopulations with the exception of the number of CD3+CD4+ cells, which in patients with CHC was larger than in those with CHB. In CHC and CHB patients, the counts of CD118+ lymphocytes were higher than those in healthy donors. Patients with CHB and those with CHC did not differ between themselves and from healthy donors in the expression of CD119 on the lymphocytes. In CHC patients, the relative CD119+ cell counts were higher between CD4+ lymphocytes than those in healthy donors. The serum levels of IFN-α and IFN-γ in CHC and CHB patients were similar, but higher in healthy donors. The concentration of IL-28B genotype in patients with CHC was twice as high as in those with CHB, but the differences were statistically insignificant. The number of lymphocytes increased with the progression of fibrosis; that of neutrophils decreased. There was an inverse relationship between platelet counts and LF severity. Multiple comparisons of the clusters of patients with different degrees of LF revealed no differences in the number of major lymphocyte subpopulations. However, the number of CD3+CD16+CD56+ natural killer-like T (NKT) cells correlated with fibrosis severity. Patients with different degrees of LF showed no differences in the proportion of CD118- and CD119 cells between lymphocytes and in the serum levels of IFN-α, IFN-γ, and IL-28B levels. Patients with grade IV LF displayed a higher proportion of CD4+CD119+ lymphocytes between CD45+ cells than did those with grade III LF. CONCLUSION: Several new clinical and laboratory trends were identified and the nature and extent of previously described hematological and immunological changes were clarified in CHC or CHB patients with various degrees of LF. Some indicators may be used as additional criteria for the prognosis of the above forms of hepatitis, and a number of newly described facts suggest that it is necessary to revise the protective/phlogogenic value of types I, II, and III IFNs in chronic viral hepatitis C and B.

[Probiotics as stimulators of immune response against pathogens in the respiratory tract].

This review analyzes whether.it is expedient to use oral probiotics for the stimulation of immune response against pathogens in the respiratory tract. It considers a relationship between.mucosal microbial colonization in different biotopes of the body and mucosal.immunity in the respiratory tract. The principal and terminological controversial issues of colonic dysbiosis and the possibilities of using the medicines and products containing live commensals/symbionts to correct microbiota disturbances are examined. There are data on the degree of resistance and resilience of the colonic microbial community exposed to destabilizing factors, antibiotics in particular. The properties of probiotics that have been proven to enhance host response against pathogens and the phenomena that characterize these probiotics as immunomodifiers and distinguish them from other immunostimulating/immunomodulating agents are described. Criteria for choosing effective and safe oral probiotics to stimulate an immune response in the respiratory tract are formulated. Finally, we review the data on the clinical and immunomodulatory effects of dietary supplement containing a combination of three probiotic strains (Lactobacillus gasseri PA 16/8, Bifidobacterium bifidum MF 20/5 and Bifidobacterium longum SP 07/3) with vitamins and minerals as an agent to prevent and reduce the severity of acute and recurrent respiratory tract infections.

[Impact of respiratory viruses on the course of chronic obstructive pulmonary disease: towards optimizing treatment].

The paper analyzes the currently available data on the impact of respiratory viruses (RVs) on the exacerbations and clinical phenotype of chronic obstructive pulmonary disease (COPD), as well as on the molecular mechanisms of this impact. It emphasizes the role of acute respiratory viral infections (ARVI), primarily rhinovirus infections (RVI) as the most important triggers of COPD exacerbations and the causes of their severe and long-term course. Particular attention is given to ARVI-induced secondary bacterial infections that worsen COPD exacerbations. The mechanisms of how RVs potentiate chronic inflammation and remodeling of the airway, which are caused by tobacco smoke, are depicted. There are arguments that there is a much greater correlation of the acute episodes showing the more severe respiratory symptoms of COPD with ARVI than can be found by molecular methods for RV verification. The body's genetic and/or acquired excessive response to viral invasion does not reflect the efficacy of antiviral defense and is an endogenous damaging factor in this situation. The role of RVs in the formation of the clinical phenotypes of COPD with frequent exacerbations remains debatable. The need for a search and more active practical introduction of means to prevent virus-induced COPD exacerbations appears obvious. In this regard, the authors identify chemical and mechanical polyvalent bacterial lysates for oral and sublingual administration. In addition to nonspecific stimulation of antiviral defense, these medicines induce antigen-specific mucosal and systemic reactions against bacterial pathogens. The role of ARVI pathogens in COPD exacerbations deserves a greater practical attention focused towards optimizing the treatment of this social disease.

Intraperitoneal Administration of Muramyl Dipeptide ß-Heptylglycoside to Pregnant and Non-Pregnant Female Mice Modulates Production of Th1/Th2/Th17/Tr1 Cytokines by Splenocytes Ex Vivo.

Muramyl dipeptide ß-heptylglycoside (C7MDP) was administered to non-pregnant CBA female mice and pregnant mice after non-abortion-prone mating (CBA×BALB/c) and mating associated with a high rate of spontaneous abortion (CBA×DBA/2). In non-pregnant females, C7MDP increased the production of IL-2, IL-4, IL-5, IL-6, IL-17, IFNγ, TNFα, and GM-CSF at constant production of IL-1α and IL-10. C7MDP increased the production of IL-10 and IL-17 and suppressed the production of IFNγ on day 8 of gestation in non-abortion-prone mouse couples and stimulated the synthesis of IL-4 and IFNγ, reduced IL-5 production, and slightly increased IL-1α secretion after abortion-prone mating. On day 14 of gestation, C7MDP elevated the yield of IL-2, IL-4, IFNγ, TNFα, and GM-CSF in CBA×BALB/c and CBA×DBA/2 couples and IL-17 in the fi rst variant of mating.

Structural changes in the thymus in allogenic pregnancy in mice with high incidence of spontaneous and muramylpeptide-induced abortions.

Structural changes in the thymus over the course of allogenic pregnancy were studied in mice from highly fertile couples (CBA females and BALB/c males), animals with high spontaneous abortions (CBA females and DBA/2 males), and in experimental immunity-dependent pregnancy loss induced by muramyldipeptide ß-heptylglycoside. Accidental involution of the thymus on days 8 and 14 of pregnancy was more pronounced in mice with high level of spontaneous embryo resorption than in females from highly fertile couples. Muramyldipeptide glycoside stimulated manifestations of thymus involution in fertile and "abortogenic" cross-breeding.