The paper estimates the efficacy of recombinant interferon α2b (Interferal^®) and γ-D-L-glutamyl-tryptophan (Bestim®) under local application to patients with chronic polypous rhinosinusitis (CPRS) based on monitoring the shift in ratio of cytokine concentrations [CIL-1RA/CIL-1β] in nasal secretions, using ELISA technique. Comparative group 1 consisted of 38 healthy people. Group 2 – 47 CPRS patients. Subgroup 2a – 21 CPRS patients who were daily administered recombinant interferon (dose of 1 million u.) injected into the polyp tissue. Subgroup 2b – 21 CPRS patients having a daily injection of interferon at a dose of 1 million u. and γ-D-glutamyl-L-tryptophan at a dose of 0.1 mg. The treatment lasted 5 days. It is found that introducing only interferon (subgroup 2a) into polypoid tissue provides a minor increase in the average ratio [CIL-1RA/CIL-1β] relative to CPRS before treatment. When interferon was introduced in combination with γ-D-L-glutamyl-tryptophan it resulted in more pronounced increase in [CIL-1RA/CIL-1β] and statistically significant (p < 0.01) increase in shifting average values of its if compared to CPRS before treatment. The presence of statistically significant difference values for subgroups 2a, 2b and group 1 shows that 5 day course results in a statistically significant shift of the ratio which should be used as an indicator of CPRS efficiency. But, the shift observed in the patient groups who had been administered immune correcting medicines does not bring the ratio value closer to that of comparative group. Therefore, the 5 day course in CPRS patients should be considered as a primary positive therapeutic indicator requiring further improvement.

A key evidence in favor of the pro-inflammatory role of glycolysis is the fact that 2-deoxy-D-glucose (2-DG), a competitive inhibitor of glycolysis, suppresses the production of different pro-inflammatory cytokines by macrophages and dendritic cells. In the present work, glycolysis in macrophages was inhibited by 2-DG or by glucose starvation (culturing of cells in glucose-free medium), both approaches being similarly efficient. When applied in normoxic conditions, glucose starvation had little effect on expression and production of tumor necrosis factor (TNF), interleukin (IL)-6 and IL-1β induced by agonists of NOD1 and TLR4 pattern-recognition receptors. By contrast, 2-DG in normoxic conditions profoundly altered cytokine production (inhibited TNF, IL-6 and IL-1β at early stages of macrophage activation as well as enhanced TNF expression at late stages). However, these effects of 2-DG were due to induction of endoplasmic reticulum stress rather than inhibition of glycolysis. Thus, literature reports about the role of aerobic glycolysis in pro-inflammatory cytokine production, particularly those using 2-DG, should be interpreted with caution. However, in hypoxic conditions, which in the present work was modelled using oligomycin, glycolysis becomes of a key importance both in cytokine production and survival of macrophages.

Abstract. The cytokine regulation of the inflammatory process in the gastric mucosa is caused ethnic characteristics of schoolchildren of the Republic of Tuva (a region with a high incidence of gastric cancer in the adult population).

The aim is study the association of cytokine levels at serum with clinical and morphological manifestations in gastritis by schoolchildren of aboriginal and foreign population of the Republic of Tuva in age groups.

Material and methods. We examined 89 schoolchildren of Tuva at the age of 7-17 years (32 aboriginal and 57 foreign). A gastroscopy was made with biopsy sampling for morphological confirmation of the diagnosis of gastritis. Diagnostics of gastritis was performed in accordance with the modified Sydney classification. Age groups was analyzed the 7-11 and 12-17 years.

Results. IL-10 in serum elevated In Tuvans with gastritis in the presence of dyspeptic manifestations at compare with Tuvans without complaints (p = 0.0253) and Europeoids with dyspepsia (p = 0.0157). Association of cytokine level with dyspepsia is not, but is with the activity of gastritis at age groups of schoolchildren of both populations. We were increase in proinflammatory IL-8 activity in antrum (p = 0.0485) and in the body of the stomach (p = 0.0485) of gastritis II-III degrees at Europeoids of 7-11 years. The level of anti-inflammatory IL-4 (p = 0.0189) was increased in young Tuvans with high gastritis activity in the body of stomach. IL-1β was decreased In Tuvans with age at gastritis with high activity in both parts of the stomach.

Discussion. The obtain data indicate about presence ethnic features of the immune response in the formation and course of gastritis. This is evidenced the dynamics of association indicators of cytokines IL-4, IL-8, IL-1β, regulating various parts of the immune system, with clinical and morphological manifestations at gastritis by schoolchildren of Tuva.

Conclusion. The features of association of cytokines IL-4, IL-8, IL-1β were installed with clinical and morphological manifestations in gastritis by children of aboriginal and foreign population of the Republic of Tuva, including depending of age.

Abstract. We investigated the effect of IL-7 on the T cell regeneration after lymphopenia induction in thymectomized mice. We showed that the recombinant mouse interleukin-7 administration in thymectomized mice was not able to compensate for the weak peripheral T cell regeneration during lymphopenia induced by sublethal irradiation. Administration of recombinant IL-7 without T cells from the thymus induced increase of the homeostatic proliferation and the phenotype conversion of the remaining radioresistant naive T-lymphocytes into central memory-phenotype T cells, the relative accumulation of the memory-phenotype T cells and possibly death of a part of actively-proliferating T cells. As a result of that events might be a progressive narrowing of T cell receptor repertoires, impaired immune surveillance and the development of cancer, autoimmune and infectious diseases.

Abstract. The search for new regulatory factors capable of activating the antitumor defense is today the flagship trend in the development of immunopharmacology. The innate immunity and NK cells, as its element, play an important role in protecting against tumor and infected cells. Muramyl dipeptides (MDPs), as a structural element of the bacterial cell wall, interact with the cytoplasmic receptors of the NOD family of human cells thereby activating the innate and adoptive immune response. GMDP-A (glucosaminylmuramyl dipeptide) is a semisynthetic analogue of MDP, which has a number of pharmacological characteristics that can be used in the clinic for the treatment of immunodeficiency states, including oncology. It is known that NK cells of human peripheral blood constitutively express NOD2 mRNA and produce its protein.

The purpose of this work is to study the effect of GMDP-A on the cytolytic activity of human NK cells in vitro, as well as on the expression of gene factors involved in the implementation of the main functions of NK cells (perforin, IFN-y and its receptors, IL-18 receptor). While studying the effect of GMDP-A on the cytolytic activity of NK cells in relation to the HT-29 tumor cell line, a 3-fold increase in cytolysis was observed with a ratio of target cells and effectors of 1:10. In addition, it was shown that GMDP-A stimulates the expression of the perforin and IL-18 receptor genes and does not affect the level of expression of the IFN-y genes and its receptors in NK cells of healthy donors. Thus, the ability of GMDP-A to activate the expression of the genes of perforin and IL-18 receptor of NK cells is shown, which combined with a significant increase in the cytolytic activity of NK cells under the influence of this agent, allows to consider GMDP-A as a promising agent to control the functional activity of NK cells in the treatment of cancer.

Abstract. The modem vaccine preparations need new safe and effective formulations, such as polyelectrolyte microcapsules, but this formulation is not studied enough to decide about its suitability in vaccines. The authors developed vaccine preparations on a base of purified antigens of the infection agents Y. pestis and F. tularensis, namely recombinant capsular Caf1 antigen and so-called acid-non-soluble tularemia complex antigen (ANCA), separately microencapsulated into the bio-compatible and bio-degradable polyelectrolyte microspheres. The antigens were obtained in the SRC for Applied Microbiology and Technology (Obolensk). A technique of co-precipitation antigens together with calcium carbonate and following layer-after-layer adsorption of the oppositely charged dextran sulfate and polyarginine onto the calcium carbonate matrix was used in the micro-encapsulation process. BALB/c and outbread mice were used in the immunization experiments. The mice were challenged with the virulent strains of the plague Y. pestis 231 or the tularemia F. tularensis 503, and the reactions of the immune system were studied including antibodies titers in the sera and expression of the immune competent cells activation markers, as far as protective effect of the immunization. The preparations were not toxic, and were capable to induce specific immunity at the level providing protectivity in some cases of the plague or tularemia challenge. The antigens associated with solid carrier such as aluminum hydroxide gel or polyelectrolyte microspheres, were more effective in the mice immunization. Authors consider polyelectrolyte microcapsules as promising delivery vehicle for vaccines.

Abstract. The study of the peculiarities of the microbiocenosis of the upper respiratory tract and cytokine profile of serum and oral fluid in children with congenital cleft lip and palate (CCLP). Children with CCLP were divided into groups according to age and stage of surgical treatment. In study we used oral fluid and peripheral blood serum obtained from children with CCLP and healthy children of appropriate age. The concentration of cytokines IL-1β, IL-6, IL-17, IL-4, IFN-γ was determined by enzyme immunoassay. For the detection of the state of microbiocenosis, bacteriological and serodiagnostic studies, the method of PCR diagnostics were carried out. The features of violations of the upper respiratory tract microbiota, characteristic of different age groups of children with CCLP, are revealed. It has been established that microbiocenosis disorders are associated with differentiated imbalances of pro-inflammatory and anti-inflammatory cytokines to a greater degree of mucosal than systemic immunity. The established changes varied depending on the degree of maturity of the immune system and the characteristics of the infectious inflammatory process associated with impaired microbiocenosis of the upper respiratory tract, and may also affect the effectiveness of the staged surgical rehabilitation of children in the CCLP. It was noted that the changes in the cytokine profile of the oral fluid in different age periods in children with CCLP were more pronounced compared to the profile of pro- and anti-inflammatory cytokines in the serum. The state of pro-and antiinflammatory cytokines of local immunity at different age periods in children with high CCLP had its own characteristics and indicated inadequate antimicrobial protection against the background of infectious and inflammatory diseases of the upper respiratory tract, different in their etiology and nature. The data indicate dysregulation of the cytokine system at the level mucosal and systemic immunity, which is closely associated with violations microbiocenosis upper respiratory tract and clinical manifestations of atypical flowing infectious and inflammatory processes in children with congenital cleft lip and palate. The obtained data substantiate the need to develop new approaches to the conduct of local target immunotherapy for correction the cytokine system at the level of mucosal immunity.

Abstract. Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in children. RSV infection, characterized by high morbidity and mortality, is a serious public health problem. There are no licensed vaccines available for the prevention of this disease. Save and affordable medications for RSV treatment were not developed yet. One of the main difficulties to study RSV pathogenesis and to develop new approaches for its therapy is the lack universal animal model that recapitulates all aspects of human pathology. There are exist animal models of RSV infection in mice, rats, ferrets, calves, sheeps, chimpanzees, etc. Most often, mice are used for RSV modeling, since their use is most economically feasible. However, RSV is not a natural pathogen for mice, therefore its replication in the mouse respiratory tract is not significant, and pathological features are poorly expressed. That is the main reason why all aspects of human RSV pathology could not be reproduced in mice simultaneously. In this study, we created the BALB/c mouse infection protocol with purified and concentrated RSV (strain A2), which allows induce such clinically significant manifestations of human pathology as bronchial hyperreactivity, pneumonia, respiratory tract infiltration by pro-inflammatory cells, etc. A study showed that RSV infection activates mainly Th1 immune response in mice, which is consistent with clinical observations in humans. Model of RSV infection in mice developed in this study can be used both to clarify the pathogenesis of the disease and to test new approaches for anti-RSV therapy.

Abstract. Neutrophils are classically regarded as cells migrating from the bloodstream to the site of infection and phagocytizing microorganisms thus providing anti-infection immunity. Currently neutrophils are characterized by diversity of functions and subpopulations. Normally, neutrophils are predominantly a homogeneous population in bloodstream. Under the influence of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), cytokines, chemokines, metalloproteinases neutrophils realize not only phagocytic and microbicidal, but also cytotoxic, cytokine-secreting, antigen-presenting, im-munomodulating, angiogenic, regenerative functions. The article reviews both the phenotypic heterogeneity of neutrophils and the diversity of neutrophil functions depending on the pathologic microenvironment: pro-inflammatory (Nl-neutrophils), immunosuppressive (G-MDSC) actions, angiogenic, atypical antigen-presenting, cytokine-secreting, inducing polarization of Th1/Th2 immune response. The participation of neutrophils in inflammatory response is considered together with additional formation of neutrophil extracellular traps and microvesicles. Neutrophilic cells death by apoptosis, netosis, necrosis/necroptosis also influence the process of inflammation progression or cessation. The possible contribution of neutrophil heterogeneity to follow up and outcome of infectious processes, autoimmune diseases, and tumors is considered. The role of neutrophils for the regeneration of organs and tissues is indicated. It was emphasized that the subpopulation composition of neutrophils is determined by functional differences and is not fully reflected by their phenotypic characteristics.

Abstract. The review is devoted to the molecular-biological mechanisms of the connection between hypoxia, inflammatory and immune processes, since it is known that lack of oxygen, on the one hand, can initiate the development of inflammation, and on the other, any inflammatory process, especially with severe systemic symptoms, is accompanied by lack of oxygen. The review provides current approaches to the connection between key transcription factor that is activated during hypoxia, HIF-1α, with the nuclear factor NF-κB, regulating inflammation. Literature data on the role in inflammation of HIF-1α activation in various types of cells and tissues, which can have both anti-inflammatory and pro-inflammatory effects, are generalized. The study of the connection between the molecular-biological mechanisms of inflammatory and immune responses and hypoxia is important not only for understanding the effects of HIF-1 on NF-κB, but also for creating potentially new therapeutic approaches to the treatment of inflammatory diseases and tumors, since HIF-1 plays an important role in their development.