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The reproductive potential of both women and men is declining every year. Many factors contribute to the violation of the reproductive function – chemical, physical, mechanical, psychogenic, however, biological factors have the most pronounced effect on reproduction. Chronic viral cervicitis can be not only the cause of infertility and reproductive losses, but also the development of intraepithelial dysplasia, as well as cervical cancer. PVI, as a monoinfection, is quite rare along with HPV. Other UGIs (urogenital infections) act as common routes of transmission and entry gates. The most common association with PVI is herpesvirus infection. An increase in MMP, both systemically and at the local level, may indicate a violation of cell modeling processes, which contributes to the development of autoimmune inflammation with further destruction of the tissues of the reproductive tract. Activation of MMP promotes the release of HSV from the nerve ganglia and reactivation of the infection. Therapy for HPV and HVI (herpes virus infections) are debatable. There is no single standard of treatment, but there are a number of drugs that have antiviral and immunomodulatory effects. Currently, there are no studies on the dynamics of the effect of HPV and HSV infection on the state of MMPs and TIMPs during Inosine pranobex therapy. Objective: to evaluate changes in matrix metalloproteinases 2 and 9 and their tissue inhibitors types 1 and 2 in patients with human papillomavirus and herpes infections after Inosine pranobex therapy. 6 patients with papillomavirus and herpetic infections were examined and treated with drugs containing the active ingredient Inosine pranobex. The levels of MMP-2, MMP-9 and TIMP-1, TIMP-2 in blood serum were determined using specific reagents from R&D Diagnostics Inc. (USA). The dynamics of indicators in the blood serum of patients with PVI showed a decrease in the level of MMP-2, MMP-9, TIMP-1 with a simultaneous increase in TIMP-2 relative to the values before therapy. In patients with PVI and HVI, Inosine pranobex therapy showed a decrease in MMP-2 and MMP-9 levels, no changes in the content of TIMP-1, but an increase in the serum content of TIMP-2. Prior to the use of therapy, an increase in the ratio in the main groups in comparison with the control group was found, however, the largest increase was found in the group with the association of infections. After therapy, positive dynamics was established in the main groups. Thus, the ratio in group I decreased and became equal to the control values. In the II group of patients, the ratio, despite the decrease, remained higher than the control values and higher in comparison with the I group of women.

According to the results of recent studies, diabetic retinopathy can be considered not only as a vascular disease, but also as a neurodegenerative process. Study of the composition of the tear fluid is used to assess the state of local immunity in the development of eye diseases. However, studies examining the effect of tear composition in diabetic retinopathy are few. The aim of the study is to determine the levels of IL-1β, IL-10, TGF-β3, MMP-7, TIMP-2, protein S100b, BDNF and NGF in the tear fluid ofpatients with vascular and neurodegenerative manifestations of diabetic retinopathy. The study included 80 patients diagnosed with type 2 diabetes which were divided into 2 groups: the 1st group included 40 patients who had no clinical signs of diabetic retinopathy on the fundus; the 2nd group included 40 patients with initial signs of non-proliferative diabetic retinopathy. All those included in the study were examined on an optical coherent tomograph RTVue-100 (USA); the volume of focal losses of retinal ganglion cells (FLV) was determined. An increase in FLV above the normative base of the device was regarded as an OCT-sign of retinal neurodegeneration. According to the results of OCT, the participants of the first and second groups were additionally divided into 4 subgroups: 1A — patients without vascular changes in the fundus and without OCT signs of retinal neurodegeneration (n = 12); 1B — patients without vascular changes in the fundus and with the presence of OCT signs of retinal neurodegeneration (n = 28); 2A — patients with initial non-proliferative DR and without OCT signs of retinal neurodegeneration (n = 10); and 2B — patients with initial non-proliferative DR and with OCT signs of retinal neurodegeneration (n = 30). The levels of IL-1β, IL-10, TGF-β3, MMP-7, TIMP-2, protein S100 b, BDNF, and NGF in tear fluid were determined by enzyme-linked immunosorbent assay. Levels of IL-1β and IL-10 in tear fluid in all subgroups were comparable to controls throughout the study. TGF-β3 content in the tear fluid of patients in the group with initial signs of non-proliferative DR (group 2) was significantly (p = 0.001) lower compared with control and group 2. However, there was no significant difference (p > 0.05) between subgroups A and B within groups. The concentration of MMP-7 in the tear fluid in all subgroups was significantly lower than in the control (p < 0.05). However, in the subgroups with OCT signs of retinal neurodegeneration (1B and 2B), the deficiency of this metalloproteinase was more pronounced (p = 0.0001). The levels of the neuropeptides under study NGF, BDNF and S100 B in tear fluid did not differ from controls in all subgroups.

The aim of the study was to evaluate the effect of sodium deoxyribonucleate on anti-infectious resistance and hematopoiesis in patients with polytraumas. A single-center study of sodium deoxyribonucleate effectiveness approved by the local Ethics Committee (protocol No. 4 05/18/2016), was conducted in 54 patients with polytrauma. The main group included 27 people, at the mean age of 39 (29-51) years old; ISS severity score, 26 (22-34). The comparison group comprised 27 people, mean age, 40 years old (26-53), mean ISS severity score was 25 points (20 to 29). The patients with randomly attributed even numbers were injected with 5 ml preparation from vials of even-numbered series, the patients with odd numbers were treated with preparation from the odd-numbered series. They were injected intramuscularly daily from day 1 to day 10 after the injury. Before treatment, as well as on days 8, 15 after injury, peripheral blood was examined for leukocyte, erythrocyte counts, hemoglobin, total protein, blood IL-6, CRP; proportion of CD117+ and CD34+ mononuclear cells, CD14+ monocytes, CD14+ granulocytes, HLA-DR+ mononuclear cells, defensin + granulocytes.On the day +8, patients from the main group, against the comparison group showed an increase in lymphocytes, monocytes, CD117+ and CD34+ cell counts. Serum IL-6 and CRP were decreased in both groups of the patients to a similar degree. Terms of hospitalization in the main group were 32.8 days, against 39.6 in comparison group. The number of complications per 1 case was, respectively, 21 versus 39, thus being 1.8 times less than in comparison group. When developing complications, anemia (Hb < 90 g/l), or hypoproteinaemia (< 60 g/l) in the main group was, respectively, 2.5and 3.5-fold less than in the comparison group.Treatment with sodium deoxyribonucleate in polytrauma may promote migration of blood precursors to the bloodstream, increase anti-infectious properties of leukocytes, reduce duration of anemia and hypoproteinemia, number of complications and decrease the terms of hospitalization.

Osteomyelitis of the lower jaw is one of the urgent problems of modern medicine. There are many reasons for the evolvement of purulent necrotic processes of the jaw bones, including the role of disorders in the systems of innate and adaptive immunity. The aim of the study was to determine the content of TNFα, IL-17, IL-4 in serum and mixed saliva in patients with uncomplicated mandibular fractures and posttraumatic osteomyelitis to determine the possibility of using these indicators for early diagnosis of posttraumatic complications. The article presents the results of a study of tumor necrosis factor α (TNFα), interleukin-17 (IL-17) and interleukin-4 (IL-4) cytokines in serum and mixed saliva in patients with uncomplicated mandibular fracture and post-traumatic osteomyelitis at the first and tenth days of observation. By means of single-layer neural networks, binary classifiers were built, allowing patients to be stratified by the clinical form of the disease and to predict its course. The probability of uncomplicated mandibular fracture is described by the ratio P = 1/(1+e-z), where the index z is determined by the level of TNFα, IL-17, and IL-4 at the first and tenth day of observation. The simulation confirmed high prognostic significance of serum TNFα and IL-17 for early verification of posttraumatic osteomyelitis, which was confirmed by the OTC and ROC indices, which varied from 87 to 100% in different models. Models 4 and 5, where TNFα recorded on the tenth day of the study was used as predictors, and a combination of TNFα and IL-17 obtained on the first day of hospitalization, were the most accurate. Modeling the results of the study of immunological indicators in the mixed saliva showed that the predictive properties have only IL-4 and IL-17, was on the tenth day of hospitalization that distinguishes these binary classifiers from similar indexes, derive from the levels of cytokines in blood serum. The results of the study indicate the important role of disorders in the system of рro- and anti-inflammatory cytokines in pathogenesis of post-traumatic osteomyelitis.

Pathogenesis studies in thyroid autoimmune diseases take a specific place among endocrine disorders, due to high prevalence of these pathologies, thus representing an urgent problem of the modern medicine. Their triggering mechanisms of their are still unknown. Changes of thyroid status in cases of nonthyroid pathology, e.g., during development of «nonthyroidal syndrome», may launch synthesis of some functionally opposite cytokines by immunocytes, with subsequent loss of tolerance to thyroid autoantigens. One may suggest that mast cells may potentially influence secretory activity of thyrocytes via Toll-like receptors, and, therefore, induce synthesis of opposite cytokines, with subsequent loss of auto-tolerance. The mast cells found in thyroid gland affected by an autoimmune disorder may also regulate functional activity of immunocytes and hormone-secreting cells due to molecular effects of secretable substances. The mechanisms prevailing in autoimmune thyroid disease are, however, widely unknown. These effects may involve either primary activation of mast cells by thyroid hormones, or secondary changes of thyroid status. To address these issues, we studied some features of mast cells response and production of functionally opposite cytokines (IL-1β, IL-10, IFNγ, TNFα) in experimental thyrotoxicosis and hypothyroidism. To boost the immune response, a subgroup of experimental animals with thyrotoxicosis was treated with recombinant interleukin-2. Specific changes of IFNγ/IL-10 ratio depending on thyroid status confirmed a role of opposite cytokine balance for development of different pathological variants. A significant increase in the Th1-marker cytokines revealed at the organ level in cases of thyrotoxicosis argued for direct involvement of thyroid hormones into the immune regulation, as confirmed by a focal infiltration of a thyroid gland with mast cells, along with significant increase in pro-inflammatory cytokines at systemic and organ levels. A hypothesis on possible reception of thyroid hormones by immune cells is in accordance with intensive correlations between the levels of opposite cytokines in target organ and contents of thyroid hormones in peripheral blood. A regulatory role of interleukin-2 was suggested as a factor of keeping balance for opposite cytokines and changing vector of immune response in case of altered thyroid status. The results of our study presume an important role of mast cells and balance of opposite cytokines in pathogenesis of thyroid dysfunction. Further studies are required, in order to clarify the mechanisms of interaction between thyroid hormones and immune cells.

AbstractDuring the COVID-19 pandemic, many questions related to the characteristics of the immune response to the disease, vaccination, and the development of post-COVID syndrome or its atypical forms remained unclear. Also, optimal and effective vaccination strategies against respiratory viral infections in the “post-COVID era” have not been determined. The variety of vaccines, vaccination history, risk factors, as well as the attachment of COVID-19 to the spectrum of seasonal infections, significantly influence the initial immunological profile of various population groups. Materials and methods. The study group included 80 young men aged 19 years living in closed communities. Blood sampling was carried out in 2022, 9 months after the course of vaccination with the Sputnik V vaccine. Pro- and anti-inflammatory cytokines (IL1β, IL4, IL6, IL8, IL10, IL17, IFNγ, TNFα), as well as IgM and IgG antibodies to SARS-CoV-2 were carried out in venous blood sera. The results were processed by Microsoft Excel, R-Statistics, SPSS 22. The normality of distribution of quantitative data was assessed by the Kolmogorov-Smirnov test. Quantitative data are presented as Me [Q25; Q75], qualitative – in the form n (%). Spearman's correlation coefficient was used to determine statistical significance. Results. Average level of SARS-CoV-2 IgG antibodies, after 9 months after vaccination exceeded the protective level by more than 3 times. Comparisons of cytokine levels and SARS-CoV-2 IgG antibodies produced varied findings. In group 1 with SARS-CoV-2 IgG antibodies

Imbalance of the proteolysis/antiproteolysis system is known to be among key components of immunofibrogenesis of liver in cases of chronic hepatitis C. To evaluate these aspects, we studied several factors of liver tissue remodeling in blood serum and local samples from HCV patients associated with liver fibrosis. We determined the levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), MMP-9/TIMP-1 and MMP-9/TIMP-2 complexes. Clinical, laboratory and instrumental examinations have been made for 81 patients with chronic hepatitis C who did not receive antiviral therapy, and 22 healthy volunteers. Extracellular matrix protein (ECM) profile was studied in 103 serum blood samples and 32 liver supernates using ELISA technique. Statistically significant increase of MMP-9 contents (p < 0.05) and its complexes with TIMP-1 (p < 0.05) and TIMP-2 (p < 0.01), as well as low levels of type 1 inhibitor (p < 0.05) were revealed in blood serum of HCV-infected patients, as compared with control group. Protein assays in liver supernates of hepatitis C patients reflecting extracellular matrix state revealed an eight-fold increase in MMP-9/ TIMP-1 complex, as compared with control group (p < 0.05). The values of other proteolytic/antiproteolytic factors proved to be low (p < 0.05). An imbalance in protease contents in blood serum and liver biopsies was revealed, showing differently directed changes. I.e., serum values of MMP-9, TIMP-1 and MMP-9/TIMP-2 during transition of liver fibrosis to cirrhosis (F0 to F4) became decreased (p < 0.05), associated with increased liver concentrations of these proteolytic enzymes (p < 0.05). In summary, we conclude that the data obtained in our study suggest an imbalance of proteolysis/antiproteolysis system leads to a dysregulated liver tissue remodeling in patients with chronic hepatitis C.

Precise mechanisms of tolerance loss to thyroid auto-antigens are still largely unknown, thus preventing further elucidation of key pathogenetic stages in autoimmune diseases affecting thyroid gland, and, therefore, to identify target pathways for treatment of these disorders. Detailed studies on the role of innate and adaptive immune cells in disturbed tolerance to autoantigens specific for thyroid gland in Graves’ disease and autoimmune Hashimoto’s thyroiditis have revealed and provided a number of theoretical foundations for arrangement of clinical immunological monitoring and forecasting of these diseases in a long-term prospective.

Expression of Toll-like receptors (TLRs) on myeloid cells is of key importance for induction of systemic reactions caused by bacterial damage, and activation mechanisms of innate immune response. The study included thirty-six patients with sepsis in whom we assessed a prognostic value of TLR2, TLR4, CD14, HLA-DR expressed on monocytes, depending on severity of the disease and clinical outcomes. There were neither significant differences in TLR4 expression at all stages of clinical observation, nor correlations between expression of this marker on monocytes and severity of the disease, or outcomes of septic conditions. Low levels of MFI on monocytes TLR2, HLA-DR at 5 and 10 days, like as decreased expression of CD14 on 10th day of the disease were shown to be predictive for poor clinical outcomes of sepsis.

Our study included measuring the following biological substances: cytokines (IL-1β, IL-6, IFNγ, TNFα, IL-10, TGF-β1, TGF-β2, IL-2, IL-17); soluble receptors to cytokines (IL-2R, IL-6R, TNFαRI and TNFαRII); total serum cholesterol; indicators of intercellular matrix degradation (metalproteinases-9; tissular inhibitor of MMP-9 1 type (TIMP-1); MMP-9/TIMP 1 and MMP-9/TIMP 2 complexes) in 260 patients with clinically manifestations of coronary and lower limb atherosclerosis. Among the patients with atherosclerosis, we have found increased average levels of IL-6, TGF-β2, TNFα RI, TNFαRII, IL-2R, along with decreased IL-2 and IL-10 concentrations, increase of MMP-9/TIMP-2 ratio in blood serum. The following direct correlations were revealed between MMP-9 and IL-1β; between MMP-9/TIMP-1 complex and IL-1β, IL-2, IL-2R, IL-17, IL-10; TIMP-1 with TNFα, IL-2 and IL-2R. At high levels of the general cholesterol, an increased production of TNFα, IL-17, TGF-β1, IL-2, IL-10, MMP-9, TIMP-1 was detected, as well as decreased amounts of TNFα I and TNFαII soluble receptors in blood serum of these patients.Direct correlations were established between total blood cholesterol levels and IL-2, IFNγ, MMP- 9, TIMP-1, MMP-9/TIMP-2. However blood cholesterol levels showed reverse correlations with TNFαRI, and TNFαRII.In the course of this study, we have specified a functional imbalance between pro- and anti-inflammatory mechanisms of immune reaction in clinically expressed atherosclerosis. Significant regulatory interactions have been revealed between cytokine levels, total blood cholesterol and markers of intercellular matrix degradation.

Abstract. Role of cytokines in autoimmune reactions in Graves–Basedow disease (GBD) is undisputable. It has been shown, that dynamic alterations in serum Th1 and Th2 marker cytokines are dependent on disease stage. At initial phase of autoimmune thyrotoxicosis, the maximal values were shown for IL-1α, IL-8, IFNγ and IL-10. A direct correlation is proven between the degree of disease severity, and the levels of proinflammatory (IL-1α, IL-8, IFNγ), as well as anti-inflammatory cytokines (IL-10), like as with production of antibodies against thyroid receptors. During conventional treatment with standard doses of thiamazol, the levels of cytokines are significantly decreased. These data extend our knowledge on pathogenetic mechanisms of the disorder. Moreover, they allow of developing an algorithm for assessment of therapeutic efficiency and probability of relapses in autoimmune thyrotoxicosis. (Med. Immunol., 2008, vol. 10, N 2-3, pp 245-250).

Abstract. Three groups of patients were investigated as follows: 1st group, HIV-infected patients, 2nd group, patients with HIV-associated tuberculosis, the 3rd group, persons with pulmonary tuberculosis. The amounts of cytokines (TNFα, IL-6, IL-10) and their soluble receptors (SRp55 TNFα, SRp75 TNFα, SR IL-6) were evaluated in blood serum by solid-phase immuno-enzyme technique. The patients did not receive antiviral therapy before, or during the investigations. Some features are revealed reflecting a direction and significance of changes in immune reactivity of the patients. In the patients with tuberculosis, IL-10 and IL-6 levels were increased, along with pronounced rise of srIL-6, relatively low index of SRp75 TNFα and deficiency of SRp55 TNFα, associated with moderate increase in TNFα. In the patients with HIV and HIV-associated tuberculosis, the direction of alterations were found to be similar, except of IL-10, i.e., a hyper-production of TNFα and its soluble type I and II receptors, increased IL-6 level in combination with lack of its soluble receptor. Correlation analysis showed a strict dependence between TNFα and viral load in the patients with IVB and V stage of HIV, and HIV-associated tuberculosis that argues for significance of TNFα in pathogenesis of HIV-infection and its progression. We have found differential trends in dynamics of cytokines under study and their soluble receptors in the course of HIV-infection progression in the groups I and II of patients, that allowing us of elaborating additional diagnostic criteria of HIV-associated tuberculosis. (Med. Immunol., vol. 10, N 6, pp 519-526).

Abstract. At present time, some conflicting data concern a possible importance of apoptosis in pathogenesis of chronic hepatitis C. A significant role is ascribed to FAS/FAS-L, as a factor of hepatocyte apoptosis. CD95+ levels at the cell surfaces were studied in liver homogenates. A significant decrease in CD95+ cells was revealed in liver samples from the patients with higher histological indexes of hepatitis activity and fibrosis. A reverse relationship between CD95+ level and local concentrations of cytokines (TNFα, IL-1, IL-10), as well as significant direct correlation with IFNγ, IL-2 values were detected, thus suggesting a failure of compensatory mechanisms of immune regulation, and predominance of anti-apoptotic viral potential over protective cellular responses. (Med. Immunol., vol. 10, N 4-5, pp 415-422).

Abstract. Sixteen children from 3 to 6 years old with complicated premorbid background, carrying S. pneumoniae, who had inflammation markers (altered IL-6 and TNFα amounts in peripheral blood analysis)тalong with immunological deficiency, were vaccinated with a «Pneumo 23» preparation. A good tolerance of «Pneumo 23» vaccine was determined. A significant increase of specific antibodies was established both to pneumococcal polysaccharides and to polysaccharides, containing in «Pneumo 23». A tendency to diminished inflammatory events and activated immunological response was revealed, that was expressed as a decrease of serum IL-6 and increase in TNFα.

Abstract. Immunopathological mechanisms of hemorrhagic fever with renal syndrome (HFRS) are very complex and are recognized as the cause of the basic pathophysiological abnormalities in this infection. In this report the results of investigation of IL12р70 and IL12р40 levels in serum of 22 patients with HFRS of different severity in dynamics of illness have been stated. High activity of IL12р70 in the acute phase of HFRS, associated with serotype Seoul virus has been determined. Probably, the influence of the other factors of immune system along with IL12р40 promoted the development of relative failure of cellular immunity in HFRS. (Med. Immunol., 2005, vol.7, № 1, pp 89592)

Abstract. With the purpose of establishment of the role of IL-4, IL-13 and IFNγ cytokines in regulation of the general IgE synthesis in serum of patients with different forms of tick-borne borreliosis, 31 patients have been surveyed. The received results have revealed that patients with ITBB irrespective of the level of the general IgE synthesis can be divided into two subgroups. In a subgroup of patients with the increased level of the general IgE, identical dynamics of proinflammatory and anti-inflammatory cytokines, describing the prevalence of the Th2 immune response has been observed. In patients with the reduced level of this antibody the mixed Th1/Th2 type and more smooth course of the illness were observed. Also, direct correlation between high level of the general IgE in serum and IgM titer was shown.

Abstract. The group of patients in amount 45 person received the standard combined therapy by preparations of recombinant IFN-α in combination with ribavirin. The positive effect of standard antivirus treatment at patients with chronic HCV-infection associated with increase of level of IL-2, decrease of levels of TNF-α, IL-1α, IL-12р40, IL-12р70 and IL-10 in peripheral serum. It has allowed to use them as noninvasive markers of the steady virologic answer during treatment of a chronic HCV-infection.