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Seasonal vaccination against influenza is considered the most effective method of specific prevention of this infection. However, in recent years, the issue of non­specific, training effects of vaccines on the immune system has been widely studied. One of the mechanisms of implementation may be a change in the production of cytokines in vaccinated people.Purpose of the study: to study the dynamics of pro­inflammatory and anti­inflammatory cytokines before and after vaccination against influenza.Materials and methods: The study involved 75 young men, the average age was 18.7±0.8 years, who were vaccinated with the Sovigripp vaccine. Those included in the study had two blood samples: (1) – before the flu vaccination; (2) – one month after the flu vaccination. Serum levels of proand anti­inflammatory cytokines were determined by solid­phase enzyme immunoassay: IL1β, IL4, IL6, IL8, IL10, IL17, IFNγ, TNFα. The results were recorded using an automatic enzyme immunoassay analyzer. Statistical processing of the obtained results was carried out using the STATISTICA 10 software package.Results: In the analysis of cytokines before vaccination, an increase in IL8, IL17 and IL6 levels was detected in 100% of cases – in 76% of cases. Within the generally accepted norms, only TNFa was determined in 92% of the surveyed population. The remaining indicators were reduced: IFNγ – in 100%, IL1β and IL4 – in more than 80% and IL10 – in 50% of cases. After influenza vaccination, there was a noticeable tendency to decrease the levels of all cytokines compared to baseline values.Conclusion: The results of the study revealed features in cytokine levels before and after influenza vaccination in healthy young people, which were characterized by deviations from the norm in both directions.

In 2019, the COVID-19 pandemic began and changed the world. Coronavirus SARS-CoV-2 has caused widespread illness and death around the world. In this regard, vaccination become the most important tool for creating herd immunity. Our study analyzed the dynamics of pro- and anti-inflammatory cytokines and antibodies to SARS-CoV-2 in the blood serum of young patients before and after vaccination against COVID-19. The study group included 76 young men. Determination of IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, IFNγ, TNFα and IgM and IgG antibodies to COVID-19 in venous blood sera was carried out twice, by ELISA using the test systems of Vector-Best Company, Novosibirsk. The first blood samples were carried out before vaccination, the second — 1 month after vaccination against COVID-19. The results were processed using STATISTICA 8.0. The vaccinated people were monitored for 6 months after vaccination. Levels of indices before vaccination: IL-1β (5.6 pg/ml (Q₂₅–Q₇₅ = 3.1–14.2); IL-4 (1.02 pg/ml (Q₂₅–Q₇₅ = 0.75–1.28); IL-6 (27.8 pg/ml (Q₂₅–Q₇₅ = 7.1–59.9); IL-8 (29.9 pg/ml (Q₂₅–Q₇₅ = 19.51–32.14); IL-10 (4.47 pg/ ml (Q₂₅–Q₇₅ = 1.84–14.75); IL-17 (7.33 pg/ml (Q₂₅–Q₇₅ = 6.82–8.58); IFNγ (0.7 pg/ml (Q₂₅–Q₇₅ = 0.4–0.9); TNFα (3.9 pg/ml (Q₂₅–Q₇₅ = 2.2–6.4). Levels of indices after vaccination: IL-1β (1.6 pg/ml (Q₂₅–Q₇₅ = 1.4- 2.2); IL-4 (0.84 pg/ml (Q₂₅–Q₇₅ = 0.59–1.12); IL-6 (1.2 pg/ml (Q₂₅–Q₇₅ = 0.6–1.7); IL-8 (10.1 pg/ml (Q₂₅–Q₇₅ = 3.8–28.9); IL-10 (5.84 pg/ml (Q₂₅–Q₇₅ = 1–9.99); IFNγ (0.6 pg /ml (Q₂₅–Q₇₅ = 0.3–0.8); TNFα (0.6 pg/ml (Q₂₅–Q₇₅ = 0.3–1.9). Both before and after vaccination against SARS-CoV-2, different distributions of cytokine levels were identified with a downward trend, but despite this, strong correlations were observed between many of them, which indicates an increase in the tension of the immune system in response to vaccination. When calculating the ratio of pro- and anti-inflammatory cytokines, its two-fold decrease was revealed, which reflects a decrease in the levels of pro-inflammatory cytokines after vaccination. The level of IgG antibodies to COVID-19 exceeded the protective level: more than 14 times in 98% of subjects. Further research into the impact of SARS-CoV-2 vaccination on innate immunity will allow us to reconsider the current vaccination strategy and determine the best approach to preventing COVID-19.

Relevance. Respiratory infections are an urgent problem for organized groups, including military ones, since the transmission of pathogens by airborne droplets and household contact routes, physical and psychological stress on adaptive mechanisms contribute to the development of the epidemic process. There is no doubt that vaccination makes a significant contribution to the prevention of respiratory infections, but the contingent remains vulnerable to other pathogens against which there are no vaccines. Therefore, the search for new methods of non-specific prevention is necessary in maintaining the health of persons permanently residing in collectives. Aim. Evaluation of the possibility of using the topical form of the recombinant interferon α-2b drug for the prevention of acute respiratory viral infections in organized groups. Materials and methods. The work was carried out according to the methodology of a multicenter (3 Centers) double-blind controlled trial involving 3,235 people aged 18 to 22 years, who were divided into three groups: 1 gy. - received a recombinant interferon α-2b (Grippferon) drug 3 drops in each nasal passage 2 times a day in for two weeks; 2 g. - saline solution intranasally according to the same scheme; 3 g. - the volunteers did not receive anything. The frequency of respiratory infections was studied. Results and discussion. Medical monitoring of the study participants, which was carried out for 2 months, showed that in the groups from the Center 1, the incidence of acute respiratory diseases for 2 months in the main group (gr. 1) was 2.3 times lower than in the control (gr. 2) and the comparison group (gr. 3). In the Center 2 The data corresponded to the dynamics of Center 1: the incidence values were 2.4-2.5 times lower in Group 1. In Center 3, the values were 2.0-2.1, respectively. The epidemic effect of intranasal administration of the topical form of the drug recombinant interferon α-2b is due to its effect on the factors of mucosal immunity, which contributes to non-specific protection and increased body resistance against respiratory infections. Conclusions. The presented advantages of the recombinant interferon α-2b drug make it possible to draw attention to the clinical feasibility of its use for preventive purposes in organized groups, including military ones, from the position of high epidemiological effectiveness, both pre-exposure and post-exposure prevention of acute respiratory viral infections.

The OBJECTIVE was choose an informative, convenient and accessible in clinical practice index for assessing the level of endogenous intoxication associated with a bacterial infection.METHODS AND MATERIALS. In the groups of patients with surgical inflammatory bacterial diseases (104 people), with intracellular non-bacterial infection (254 people), and in healthy people (94 people), the degree of LII correlation according to Kalf-Kalif (as a "standard" of indices) was compared with more simple and easy-to-calculate indices: LII according to Ostrovsky, simplified LII according to Ostrovsky ¬ without taking into account plasma cells (sLII according to Ostrovsky), the blood leukocyte shift index according to Yabluchansky, the Harkavy index and the Krebs index.RESULTS. Within all groups of observations, the closest correlation with LII according to Kalf-Kalif was established for LII according to Ostrovsky, slightly less for LII according to Ostrovsky. The latter was chosen for further study due to the possibility of calculation based on the data of the 5diff automatic blood cell analyzer. Compared with the group of healthy people (1.34 (0.93; 1.59)) sLII according to Ostrovsky did not increase in the group of patients with intracellular non-bacterial infections (1.21 (0.82; 1.49)), moderately increased in subgroup of urological and gynecological patients with chronic local inflammatory processes (2.35 (1.49; 2.99)) and was many times higher in subgroups with acute inflammatory and destructive diseases of the abdominal organs (7.64 (2.05; 11.77 )), sepsis (8.58 (2.96; 13.29)) and septic shock (7.34 (4.07; 9.48)).CONCLUSION. The calculation of LII according to Ostrovsky or its simplified version without taking into account plasma cells (neutrophils + immature granulocytes)/(lymphocytes + monocytes + eosinophils + basophils) is appropriate and easily applicable in wide clinical practice for assessing a bacterial infection and the development vector of an infectious process.

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.

Purpose. To detect the levels of transform growth factors-β (TGF- β1, TGF- β2, TGF- β3), interferon-ʏ (INF- ʏ), matrix metalloproteinase-9 (MMP-9) and S100B protein in blood serum of patients with type 2 diabetes mellitus (DM) and to reveal the connection of these factors with neurodegenerative changes in the retina. Material and methods. 30 patients, averagely aged 60.3, with type 2 DM and no signs of diabetic retinopathy (DR) (the main group) and 30 healthy individuals (control group) were examined using microperimetry and optical coherence tomography. A sandwich variance estimator of solid phase enzyme-linked immunosorbent assay was used to determine the levels of TGF- β 1, TGF- β2, TGF- β3, INF- ʏ, ММР-9 and S100B protein in blood serum of the subjects examined. Results. The patients with type 2 DM were found to experience an increased level of focal loss of retinal ganglion cells and a drop in the average photosensitivity of the retina. The main group also showed a reliable increase in the level of S100B protein and in the serum level of MMP-9 against the control, but no significant difference between the groups was found in the level of TIMP-1. The level of TGF- β2 was significantly higher in the main group, which also showed a deficiency of TGF- β3. No significant difference was found between the two groups in the levels of TGF- β1 or INF- ʏ. In contrast, a positive correlation was revealed between the levels of S100B, MMP-9 and the volume of focal loss of retinal ganglion cells. Conclusion. Patients with type 2 DM and signs of neurodegeneration of the retina reveal a higher activity of some cytokines and MMP-9. This may indicate an important role of neuroinflammation and dysfunction of the immune system in the retinal neurodegeneration process of DM patients. Further research of other cytokins is required to determine early and more sensitive markers of retinal neurodegeneration.

An effect of the antiviral drug Kagocel on the levels of metalloproteinases MMP-8 and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in induced sputum during treatment of community-acquired viral-bacterial pneumonia was analyzed. 60 adult patients with verified community-acquired pneumonia of viral-bacterial etiology were included in the follow-up monitoring. Materials and methods. All patients were randomly stratified into 2 groups: group 1 (comparison group) consisted of 30 patients receiving Ceftriaxone monotherapy; group 2 (main group) 30 subjects who were prescribed Ceftriaxone and the antiviral drug Kagocel as etiotropic treatment. Both groups were comparable in gender, age and time of admission to the hospital. Results. During hospitalization, patients in both groups had elevated levels of MMP-8, MMP-9, TIMP-1 and TIMP-2 in induced sputum compared to the reference values. By 7 days of inpatient treatment, the level of MMP-8 was still significantly higher than the reference values in both groups, being in patients from group 2 it decreased compared to baseline values, whereas in patients from group 1, on the contrary, it was markedly elevated. The activity of MMP-9 during hospitalization was also high in patients from both groups compared with its level in healthy subjects. By day 7 of therapy, changes in various parameters were recorded. The level of MMP-9 in patients from group 1 increased, whereas in group 2 on the contrary decreased. The level of TIMP-1 decreased in patients of the 1st group below the control value, and in patients of the 2nd group reached the reference values. The level of TIMP-2 decreased in both groups and reached that of in control group. Conclusion. Antiviral drug Kagocel being included in the standard antibacterial regimen of community-acquired viral-bacterial pneumonia reduces the level of MMR-9 and intensity in imbalance between MMP and TIMP parameters by 7 days of therapy, which leads to accelerated clinical recovery.

The present study focuses on the comparative assessment of the therapeutic efficacy of the antiviral drugs riamilovir and umifenovir in the treatment of patients diagnosed with influenza. The aim of the study was to compare the clinical efficacy and safety, as well as the incidence of complications, of the use of antiviral drugs riamilovir and umifenovir and the use of only symptomatic therapy in patients with a confirmed diagnosis of influenza. All patients were hospitalized at the Regional Clinical Hospital No. 2 in Vladivostok. The study included 150 patients, who were divided into 3 groups (50 patients in each group), comparable in gender, age, and admission to the hospital. Patients of the first group received riamilovir, the second group received uminofenovir, patients of the third group received only symptomatic therapy (control group). The duration of clinical manifestations of the disease, hematological disorders, as well as the content of cytokines TNF-α and IL-10 in blood serum were assessed. The incidence of complications in each group was taken into account. As a result of the study, it was found that the inclusion of the antiviral drugs riamilovir and umifenovir in the therapy of influenza decreases the amount of the pro-inflammatory cytokine TNF-α after 5 days of treatment; and in case of symptomatic therapy its level significantly exceeded the reference values. The level of anti-inflammatory cytokine IL-10 on the 5th day of treatment in the main group was three times lower than in the control group. Thus, riamilovir and umifenovir effectively relieve the main symptoms of the disease, reduce the incidence of complications, and reduce the severity of the inflammatory response by the 5th day of treatment.

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.

The neuropeptides comprise an important part in the nervous system interacting with endocrine and immune systems. Peptide regulators are responsible for the continuity of communicating elements, which support homeostasis, however, despite abundant research examining neuropeptides, not all specific mechanisms and features of interacting proteins with cells and immune components have been uncovered. Objective: to perform a comprehensive assessment of neuropeptide system in patients with herpes zoster. Materials and methods: 106 in-hospital patients were examined diagnosed with herpes zoster within 2016–2019 period. Control group consisted of 30 healthy age- and sex-matched volunteers. Blood serum was collected after verifying diagnosis on day 1. After discharge, patients were monitored for signs of pain syndrome and overall state within 3 months. It allowed to divide patients into 3 groups retrospectively. Group 1 — patients with herpes zoster, accompanied by mild or moderate pain syndrome; group 2 — patients with herpes zoster, accompanied by severe pain; group 3 — patients with herpes zoster, complicated by postherpetic neuralgia. Level of serum protein s100B, myelin basic protein, nerve growth factor, brain-derived neurotrophic factor, neuron specific enolase was measured by using specific reagents purchased from “R&D Diagnostics Inc.” (США). Results. it was found that level of serum protein S100B in all groups was significantly increased compared to control group, showing no inter-group differences. Amount of myelin basic protein in all study groups vs. control was significantly higher. Moreover, level of these parameters in group 2 vs. group 1 and 3 was significantly elevated. In addition, level of nerve growth factor was significantly increased in group 1 vs. groups 2 and 3, whereas in group 3 it was significantly lower than in control and group 2. Brain-derived neurotrophic factor was significantly decreased in all the study groups compared to control, showing no significant intergroup differences. Level of neuron-specific enolase was significantly increased in group 3 vs. control as well as group 1 and 2. The data obtained allowed to identify two parameters for assessing a risk of postherpetic neuralgia in acute herpes zoster, as well as provided deeper insights into the pathogenesis of neuroimmune disorders accompanying herpes zoster.

Relevance. Currently, the development of vaccines against COVID-19, their clinical trials are actively continuing, and the effectiveness of the vaccines used is being analyzed. A very important issue will be how and when to vaccinate patients with various chronic diseases, what are the relative and absolute contraindications for vaccination, how various diseases can affect the effectiveness of vaccination.Aims. To present an overview of the most significant published materials on the issue of vaccination against COVID19 patients with allergic diseases, as well as the likelihood of developing adverse events of an allergic nature in response to the introduction of the vaccine. Conclusions. An active study of vaccines, their effectiveness and safety, demonstrates to us the high reliability of these drugs and the absence of high risks of adverse events in comparison with other vaccines. Anaphylactic reactions to the introduction of COVID-19 vaccines are not more common than for any other vaccines used in international medical practice.

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.

Interleukin-2 (IL-2) is one of the most important cytokines involved in the regulation of innate and adaptive immunity. Its main immunological function is to regulate a specific (antigen-dependent) immune response by stimulating proliferation and differentiation of immune cells involved in its realization, including Т-lymphocytes. Dysfunction of cellular immunity is the main pathogenetic mechanism for the development of HIV infection.Objective: to identify patterns of IL-2 levels change in HIV-infected patients on the background of drug resistance at the later stages of infection. The study included 83 patients with HIV infection receiving highly active antiretroviral therapy; the control group consisted of 20 healthy blood donors. All patients underwent a study of the effectiveness of antiretroviral therapy, including an assessment of HIV viral load and CD4+ Т lymphocyte levels. In patients with ineffective antiretroviral therapy, a study of drug resistance to HIV by Senger sequencing was additionally conducted. According to the results of genome sequencing, HIV-infected patients with ineffective antiretroviral therapy were divided into two subgroups — with revealed drug resistance (58.5%) and absence of detectable resistance mutations in the genome (41.5%). Levels of IL-2 were measured in all persons included in the study by the method of enzyme immunoassay. When comparing the levels of IL-2 between groups of patients with continuing viral load on the background of antiretroviral therapy (viral load is detected) with drug resistance and without it, significant differences were obtained (1.75±0.26 pg/ml versus 1.95±0.29 pg/ml, p ≤ 0.05, U-criterion, respectively). The content of IL-2 is statistically significantly lower in the group of patients who did not succeed with antiretroviral therapy than in the group of patients with treatment efficacy (1.83±0.29 pg/ml versus 4.89±0.55 pg/ml, respectively, p < 0.001, U-criterion). Thus, it is shown that in patients with revealed drug resistance against the background of progression of HIV infection there is a decrease in levels of IL-2. The increase in its levels in patients with HIV infection who have reached virological and immunological success of therapy is due to the reduction in the number of the cytokine-producing immune cells (T-lymphocytes). We assume that a significant decrease in the levels of IL-2 makes an additional contribution to the disruption of the processes of proliferation and differentiation of immunocompetent cells in HIV infection, which is of great importance in the formation of drug resistance of HIV in conditions of constant viral replication.

The article features the effectiveness of different psychotherapeutic approaches to psychological care in order to determine the most effective type of psychotherapy for depressive and anxiety disorders. The research considers the place of anxiety and depressive disorders in the ICD-10 classification; the article notes a contradiction between the theoretical separation of these disorders in ICD-10 and the frequent comorbidity (50 %) of these disorders in the clinical picture; the authors justify the choice of one form of psychotherapy for disorders of the anxiety-depressive spectrum. The paper contains an overview of the results of meta- analyses for person-centered, psychodynamic, cognitive-behavioral psychotherapy. It describes and analyses the most common approaches to psychotherapy of anxiety-depressive spectrum disorders by applying combined pharmacotherapy and psychotherapy in the cognitive-behavioral and interpersonal approaches. Based on the overview of meta-analyses of evidencebased studies of the effectiveness of these types of psychotherapy, it is concluded that short-term interpersonal and cognitive-behavioral approaches are most preferable in the therapy of anxiety and depressive disorders. There is a tendency towards further integration of approaches on the methodological basis of cognitive-behavioral therapy.

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. Chronic hepatitis C antiviral therapy should be followed by immune rehabilitation measures directed to T-cell immunity stimulation and elimination of circulating immune complexes. The dynamics of concentrations of molecular fractions of circulating immune complexes and immunoglobulins has been studied. Moreover, phagocytosis indices were evaluated during combined antiviral therapy by standard PEG-interferon and ribavirin and immuno correction drag Ronkoleukin. Application of Ronkoleukin in combination with antiviral therapy determines possibilities to optimize existing treatment protocols of chronic hepatitis C.

Abstract. In the last years immunological aspects are studying in the pathogenesis of infectious diseases. The influence of immune response to the infectious processes of acute and chronic virus infectious (Hemorrhagic Fever with Renal Syndrome and Chronic Viral Hepatitis C, as an example) has been revealed. Misbalance of system and local cytokine status characterizes the direct influence of immune system to all organs and systems of human organism. It determines the severity of the disease and its outcomes.

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.

The changes of the cytokines and lipidic spectrum at experimental hyperlipoidemia and arterial hypertensia was made at 20 rats «Vistar» during 6 months. As the material of research was the blood serum. The cytokines was made by the method solid-phase not competitive immune-enzyme analysis with the use of sets: Rat «R&D Diagnostics Inc.», USA. The content of the general cholesterol; triglycerides; LDL; HDL was investigated by the method of standard colorimetric analysis with the use of reagents «Olveks diagnosticum» (Russia). The increasing of the general cholesterol, LDL; HDL, atherogenic coefficient, IFN-γ and IL-1β in blood of animals was revealed. At application of immunomodulator «Galavit» at experimental atherosclerosis the decreasing contains of IL-1, IFN-γ, the level of general cholesterol; LDL; HDL, atherogenic coefficient is fixed.

In view of abundance of autoimmune diseases of thyroid, gland, Graves' disease in particular, the role of immune regulation and the possibility of controlling it by estimating the function of regulatory T-limphocytes are important questions today. Available for practical estimation of T- and B-lymphocytes tolerance disorder in GBD are serum, levels of Th1-and Th2-marker cytokines. Experimental exogenous thyreotoxicosis in Wistar rats showed significant increase in serum Il-1β, IFN-γ and Il-10 depending on the increase of thyroid hormones, as well as significant changes in correlation between pro-and anti-inflammatory cytokines with the shift towards Th1-marker cytokines in supernatant thyroid glands of the animals with thyreotoxicosis.

In 51 patients, immune status was assessed before and after coronary aortic bypass graft (CABG) surgery. All participants were divided into two groups: Group I - without any post-surgery complications (n=23; 45,5%); Group II - with post-surgery infectious and inflammatory pathology (n=28, 54,5%). Cardiosurgery patients had immunocompetent cell distribution pathology, which reflected immunity status abnormalities. Functional cell activity was decreased, humoral immunity was disturbed. In patients with septic complications, these disturbances were observed before CABG, and after the intervention they were even more severe. Immune disturbances in cardiosurgery patients play an important part in post-operative complications' pathogenesis, and ask for active risk factor screening, as well as for preventive immunotropic therapy.