In 2018, we celebrate the 120th anniversary of Academician, Professor Vladimir I Ioffe, a leading figure of national immunology. The world-level achievements of V.I.Ioffe in research, his undisputed priority in the most important areas of fundamental immunology are worth of recognition and interest among the immunologists. V.I.Ioffe was far-seeing and precise in his scientific prescience. He has authored a number of discoveries which were proved to be of fundamental and practical significance over 50 succeeding years. The scientific contribution of V.I.Ioffe is considered equal to achievements of the most illustrious Nobel Prize winners. Academician V.I.Ioffe regarded the immune pathology as a next step in development of general immunology, thus allowing applications of general fundamental immunology to the tasks of immune pathology. Vladimir I. Ioffe is rightly seen as a founder of native clinical immunology. He has formulated the tasks of clinical immunology as based on interests and requirements of clinicians.  Vladimir I.Ioffe has presented a condition which he related to any study in clinical immunology, i.e., a need for comparisons between the results of immunological testing and clinical course of the disease. All the requirements in immune laboratory diagnostics, having been proposed and established by the Academician Vladimir I. Ioffe, have kept their significance up to the present day.

ApoE is a member of lipoprotein family. It is the most common lipoprotein in the central nervous system (CNS), secreted by astrocytes, microglia, neurons and immunocompetent cells, including lymphocytes, monocytes and macrophages. According to recent data, it has endotheliotropic and immunomodulatory functions, regulating inflammatory activation of mononuclear phagocytes and antigen-induced lymphocyte proliferation. APOE4  allele is a major genetic risk factor of Alzheimer’s disease, with prevalence 3-12 times higher in those who have this allele. Mechanisms that predispose carriers of the allele to earlier clinical presentation of neurodegeneration include changes in lipid metabolism in the CNS, in the buildup of neurotoxic amyloid-beta oligomers, in the clearance of amyloid-beta peptides from the CNS and in regulation of immune response. In this review the functions of ApoE protein in central nervous and immune system and changes in functional activity of the protein in APOE4 carriers are discussed. The impact of APOE4 allele on monocyte phenotype and inflammatory activation of monocytes, on specific cell-mediated immune response to amyloid-beta antigens and on effectiveness of immunomodulatory therapy in patients with Alzheimer’s disease summarized, as well as the possible role of changes in the immune response characteristic for APOE4 carriers in the increased risk of Alzheimer’s disease.

Our understanding of anticancer immune surveillance currently serves as a basis for development of novel therapies that utilize patient’s own immune system as an anticancer agent. Previously, cancer immunotherapy mostly included non-specific immunomodulating agents, cytokines, or cancer cell-based tumor vaccines. Emerging understanding of diverse interactions between the immune system and cancer cells allows to develop novel, more effective therapeutic approaches that target only specific populations of immune cells. Recent studies focus on testing efficiency of allogenic and authologous anticancer immunity, strategies for ex vivo expansion of these cells, and approaches to increase their anticancer activity and specificity. Most recent approaches focus on re-targeting immune cells to specific tumor antigens, shifting the balance of immunosuppressive tumor microenvironment towards immune stimulation and utilizing immune cells to target tumor architecture. This review is focused on the prospects of different immuno-therapeutic strategies.

Visceral obesity, dyslipidemia and insulin resistance are considered the main causes of metabolic disorders in metabolic syndrome. Leptin and ghrelin are the most important factors involved in regulation of the metabolic processes. The purpose of this study was to evaluate the significance of leptin-to-ghrelin ratio (L/Gh) and cytokine profiles as biomarkers of metabolic and immune disorders in an in vivo model of a dietary induced dyslipidemia in mice.

The studies were carried out on 48 female C57Black/6 mice, which were divided into 6 groups of 8 animals. Group 1 (control) received the AIN93 diet; group 2, excess fat administration (30% dry weight); the mice from group 3 were supplied with 20% fructose in drinking water added to the main diet; group 4 got fats and fructose excess, group 5, cholesterol excess (0.5% dry weight); group 6 was fed with cholesterol and fructose in excess. Duration of the experiment was 63 days. In all animals, the relative mass of internal organs was determined. The levels of cytokines, leptin and ghrelin in plasma were determined by means of Luminex 200 analyzer using Bio-Plex kits.

There were no significant differences for plasma leptin and ghrelin concentrations between the control and most of experimental groups, except of the 6th group (combined diet with excess fructose and cholesterol) which a significantly lower leptin levels as compared to the controls (group 6: 2.12 pg/ml, min 1.57 – max 3.83 vs group 1: 3.92 pg/ml, min 2.45 – max 27.88, p < 0.05). The changes in plasma ghrelin contents, depending on the diet, showed a generally opposite trend when compared to leptin levels.

The value of L/Gh ratio in mice fed with excess fat (group 2) and cholesterol (group 5) showed a statistically unsignificant trend for increase. Fructose added to a diet with fat or cholesterol excess caused a significant decrease in L/Gh ratio (p < 0.05). In animals of the 6th group (fructose + cholesterol) with minimal L/Gh values, the lowest total body fat deposition was found. The relationship between the L/Gh and the fat mass was confirmed by the linear regression relationship between the indicators considered. We have also found a correlation between L/Gh and animal fat weight (r = 0.424, α = 0.004), relative mass of adipose tissue (r = 0.663, α = 0.000), liver (r = -0.315, α = 0.035) and spleen (r = -0.585; α = 0.000), statistically significant correlations between L/Gh, organ and tissue weight and concentrations of IL-12(p40), IL-2, IL-9, IL-13, G-CSF and RANTES. In addition, significant differences were found between the control and test groups for plasma concentrations of G-CSF, IL-12(p40), IL-2, IL-3 and IL-9. The IL-12(p40) concentration in plasma from the group 2 mice was the lowest against controls. Meanwhile, the 6th group exhibited highest IL-12(p40) levels against the lowest L/Gh ratios and total fat levels.

Thus, a significant relationship was found between L/Gh ratio and changing mass of organs and tissues, as well as with the levels of cytokines involved into the regulation of inflammation. The most significant relationship was found between the relative mass of body fat, L/Gh ratio and the IL-12(p40) concentration. L/ Gh ratio and IL-12p(40) showed both content Not only a correlation dependence, but also significant changes were noted between the experimental groups in the in vivo model of alimentary dyslipidemia in mice.

Dendritic cells (DCs) of patients with high-grade brain glioma exhibit impaired expression of membrane TNFα associated with low DC cytotoxicity against TNF-R1-expressing tumor cell line HEp-2. To assess the significance of these findings, we investigated a role of TNFα/TNF-R1-signaling pathway in DC cytotoxic activity against allogenic and autologous cell lines obtained from high-grade glioma tissues. DCs were generated by culturing of plastic-adherent peripheral blood mononuclear cells in presence of GM-CSF and IFNα for 4 d followed by LPS addition for 24 h (IFN-DCs). The tumor cell lines were obtained from tissues of 11 patients with glioblastoma multiforme. According our findings glioblastoma cells were sensitive to lysis mediated by donor IFN-DCs. The level of DC cytotoxic effect against cell lines obtained from different glioma patient tissues varied from 20 to 72.2%. DC lysis of 8 out of 11 glioblastoma cell lines exceeded 40%. Glioblastoma cell lines expressed both TNF-R1 and TNF-R2 receptors, but mostly – TNF-R1. However, rTNFα did not show cytotoxic activity towards glioblastoma cell lines. Blocking of TNFα/TNF-R1-signaling pathway by treating of donor IFN-DCs with soluble rhTNFR1 receptor led to partial decrease of DC cytotoxic activity against 5 out of 6 tested glioblastoma cell lines by 11-40% (median of suppression 24%). Glioblastoma patient IFN-DCs which were characterized by an impairment of TNFα/TNF-R1-signaling pathway lysed these glioblastoma cell lines, however median of DC cytotoxicity was 30% lower than that of donor values (31.5 vs 45.1%; р = 0.003). Cytotoxic activity of IFN-DCs of the glioblastoma patient against autologous tumor cells resistance to TNFα/TNF-R1-signaling pathway was comparable with level of cytotoxicity of donor IFN-DCs. Thus, glioblastoma cells are sensitive to cytotoxic activity of DCs mediated via TNFα/TNF-R1-signaling pathway, but the defect of this mechanism in IFN-DCs of glioblastoma patients determines significant decrease of DC cytotoxicity towards glioblastoma cells.

The paper presents results of studying systemic and local level of cytokines in retinal vein occlusion following antiangiogenic therapy. The study of cytokine concentrations was conducted in the general group of patients, and depended on the type of retinal vein occlusion before and after intravitreal injections of Ranibizumab. We examined thirty-two patients with retinal vein occlusion. We performed standard ophthalmological examinations, spectral optical coherence tomography, fluorescent angiography in order to establish the type of retinal vein occlusion. We determined concentration of vascular endothelial growth factor (VEGF), endothelin-1, interleukin-1, interleukin-6 and tumor necrosis factor-α in serum and tears by enzyme immunoassay before treatment, and 3 months after regular injections of Ranibizumab. The obtained data prove that all the patients with retinal vein occlusion had significantly increased VEGF levels in blood serum and tear fluid compared to the control group. We have revealed a positive correlation between levels of VEGF in tear fluid, and interleukin-1, interleukin-6 and endothelin-1 in the tears, as well as with VEGF concentrations and endothelin-1 in serum. We have found an increase of endothelin-1 in tear and serum, alongd with interleukins and tumor necrosis factor-α in tear fluid, with maximal concentrations of some factors in ischemic type of retinal vein occlusion. Following antiangiogenic therapy in patients with non-ischemic type, there was a significant decrease in VEGF level, interleukin-6 and tumor necrosis factor-α in the serum, vascular endothelial growth factor and interleukin-1 in tears. In patients with ischemic type, a significant decrease in VEGF and interleukin-6 concentrations in tears, endothelin-1 and interleukin-1 in blood serum. Thus, our research showed the role of interleukins, tumor necrosis factor-α, vascular endothelial growth factor and endothelin-1 in pathogenesis of retinal vein occlusion.

The history of dermatology reminds a lot of attempts to transform the dense human skin samples into a liquid phase. A search for a method aimed to separate cellular substrate of the skin and to obtain a suspension for studying the cell phenotype profile was a basis of our long-term study, which resulted in a proprietary method for digital estimation of distinct subsets composing the skin cell population. The skin cytoimmunogram is the name of the invention, which is recognized as practical and promising for implementation in public healthcare system as recognosed by the decision of the “Xth International Conference of Immunologists of the Urals”, where the report on the “Prospects for application of the skin cytoimmunogram” was presented for the first time. The results of a single case analysis showed the following findings for this skin sample: 1) a subpopulation of keratinocytes is actively represented, most of them activated, which indicates a moderate proliferative activity of the basal layer of the epidermis; 2) there are B-lymphocytes, which normally are residents of the circulating blood and lymph, since they have a positive taxis to the high endothelial venulas located mainly in the lymph nodes. Their presence in the skin indicates the activity of humoral immunity; 3) presence of several T-cell types of (CD⁺3 lymphocytes) localized predominantly in the three outer layers of the epidermis, and the findings of CD4⁺ cells predominating over CD8⁺ cells suggests an increase in adaptive skin immunity; 4) low content of T-cytotoxic cells indicates to absence of an infectious/inflammatory process; 5) the remaining parameters reflect the numbers of specific skin cells, characterized by low activation grade, which, along with absence of specific complaints in this patient, indicates to normal state of his skin; 6) cell viability in the native sample was 99.8%, after cryopreservation – 87.0%. The proposed method allows to obtain information on the quantitative composition and functional activity of skin cells, which distinctly indicates to the present condition of the patient’s local immunity and may become a basis for development of personalized curative and prophylactic programs. The Сytoimmunogram of skin as a way of skin diagnostic evaluation, is easy to implement, and it is available for qualitative and quantitative evaluation of separate cell subpopulations, in order to assess their function and degree of their response to any external or internal environmental impact. Widespread application of the сytoimmunogram perspective will allow to create sex- and age-matched registry for skin parameters in normal and pathological conditions, thus determining the extent of skin response to environmental exposures, to measure activities of cell subsets in native skin under normal and pathological conditions, to justify the criteria of age-related skin changes, to objectively assess clinical course of skin diseases, and to individually select the drug and monitor the effectiveness of external medical drugs applied.

To identify new effective targets for immunotherapy of breast cancer, based on cancer-testis antigens (CTA), the associations were studied between CTA gene expression, clinical and pathological characteristics of breast cancer. Therefore, the aim of the study was to perform screening of CTAs specific to breast tissue tumors (luminal types A and B) based on assessment of the transcriptional profile of cancer-testis genes in the patients of different ages. To evaluate these relations, paired surgical biopsies (normal and tumor) of breast tissue of 32 patients (64 samples) aged 38-86 years were used. Relative expression of 16 genetic loci (MAGEA1, MAGEA2, MAGEA3, MAGEA4, MAGEB1, MAGEB2, GAGE1, GAGE3, GAGE4, MAGEC1, BAGE, XAGE3, NY-ESO1, SSX2, SYCP1 and PRAME1) was determined by the RT-qPCR. It was found that the transcriptional profile of CTA differs in different age groups of patients (at the age of < 55 years, overexpression of MAGEA3 was noted; after 55 years, MAGEA1, MAGEB1, BAGE, NY-ESO1, GAGE1 and GAGE3 were more expressed). In the luminal type A cancer, overexpression of MAGEA1, MAGEA2, MAGEA4, MAGEB1, MAGEB2, GAGE3, GAGE4, MAGEC1 and PRAME1, whereas in B type cancer, the genes with increased expression were not detected. These differences should be considered when planning immunotherapy, can be used as biomarkers for both breast cancer as clinical entity, and, in particular, for its individual subtypes.

The aim of the study was to investigate activities of NAD- and NADP-dependent dehydrogenases in peripheral blood lymphocytes of the patients with renal cell carcinoma (RCC) at the terms before surgery and 14 and 30 days after surgical treatment. The patients at the age of 45-55 years with locally advanced RCC were examined before surgical treatment, 14 and 30 days after surgery. The control group consisted of healthy donors of the same age range. Activity of NAD- and NADP-dependent dehydrogenases was determined by bioluminescence method using bienzyme complex isolated from luminescent bacteria. The enzyme profile changes of peripheral blood lymphocytes in the patients with RCC in pre- and postoperative period have been revealed. The lymphocyte metabolism in patients with RCC at the pre-operative period was characterized by decreased activity of pentose phosphate cycle, and glutathione-dependent antioxidant system. The changes in activity of these processes may lead to decreased levels of macromolecular synthetic reactions in the lymphocytes and activation of peroxide reactions. We have registered a decreased activity of lactate dehydrogenase anaerobic reaction which characterizes inhibition of the terminal anaerobic glycolysis reactions. The levels of metabolic reactions in blood lymphocytes from the RCC patients in preoperative period determining the intensity of aerobic respiration corresponded to control values, along with an increased intensity of the NAD-dependent substrates outflow from the tricarboxylic acid cycle to the amino acid exchange reaction. In the postoperative period in patients with RCC in blood lymphocytes the activity of the terminal reactions of the anaerobic glycolysis hold on, the aerobic lactate dehydrogenase reaction moderately activated. During the entire postoperative period, an increased outflow of NAD-dependent substrates from the tricarboxylic acid cycle to the amino acid exchange reaction is registered in blood lymphocytes of RCC patients. Nevertheless, there is a significant increase in the intensity of the Krebs cycle terminal reactions, which determines an increase in aerobic respiration activity being energetically more beneficial to the cells. At the same time, «impoverishment» of the pentose phosphate cycle metabolites in the lymphocytes of the patients with RCC, due to similar redistribution of the substrate flows, leads to decreased plastic processes in cells. Even 30 days after surgical treatment, a decrease remains in glutathione-dependent antioxidant protection of the cells. Therefore, the patients with RCC need correction of metabolic processes in the immune cells during postoperative period. This fact should be taken into account by developing rehabilitation programs in this category of the patients.

The aim of the study was to determine efficiency of Glutoxim, aimed for correction of immune disorders. The drug was administered to the patients with chronic cerebral ischemia (CCI, Stage I and II) complicated by arterial hypertension. Increased contents of pro- and anti-inflammatory cytokines, IFNγ, IL- 2, G-CSF, and activation of the complement system have been revealed for these conditions, at both functional stages of the disease. The patients with stage II CCI showed elevated markers of oxygen-dependent activity in polymorphonuclear leukocytes (increased levels of spontaneous and stimulated nitroblue tetrazolium (NBT) reduction tests, phagocytic capacity and stimulation index of neutrophils). Stage I of chronic cerebral ischemia was characterized by normal values of NBT reduction tests and functional reserve of neutrophils, along with decreased stimulation index of neutrophils. Among 26 parameters of immune status, 73.1% and 80.8% of indices proved to be changed, respectively, in the patients with stage I and II CCI. 66.7% of immune indices appeared similar in magnitude and direction of changes, whereas the resting 33% are identical in orientation. Usage of Cereton and Actovegin in treatment of the stage I CCI caused normalization of 5.3% immune parameters, with partial normalization of 26.3% tests, and 68.4% of the indexes remaining unchanged or increased posttreatment. Inclusion of Glutoxim into the combined pharmacotherapy proved to be more effective since it totally normalized 52.6% of the indexes, along with partial normalization of 21.1%, while 26.3% of the indicators were not affected by the therapy. Administration of Cereton and Actovegin at the second stage of chronic brain ischemia was followed by partial normalization for 47,6% of the tests, while leaving unchanged or increased 52.4% of the indicators. Glutoxim Use fully normalize 19.0% and partially normalizes 57.1% of immune parameters.

Erysipelas is an actual problem of health care. It is characterized by consistently high morbidity, excepted tendency to recur, reduced the life quality and took important place in the structure of temporary disability. The changes of immunological reactivity, depended on genetic characteristics of the individual were established to play important role in the pathogenesis of erysipelas. The prediction of the course of erysipelas is unresolved problem yet. The genetic features of the organism, such as the genetic polymorphisms of some cytokines, involved on the prediction of the course of erysipelas. Investigations of TNFα genes demonstrated that their transcriptions increased and productions enhanced. Aim was to study the influence of polymorphism of TNFα gene promoter rs1800629 on the concentration of TNFα in the blood of healthy individuals and patients with erysipelas in primary and recurrent course. The study was performed at 104 patients with erysipelas (54 patients with primary erysipelas and 50 patients with recurrent course) and 94 healthy residents. Gene polymorphism of TNFα rs1800629 was detected by PCR method. Measurement of the concentration of TNFα was performed by immunoassay analysis. Homo- and heterozygous SNP of the TNFα rs1800629 gene were conformed to Hardy–Weinberg equilibrium (p > 0.05). Minor allele A was found to be registered in erysipelas patient less frequently by 2.9 times than in healthy individuals. The patients who carried homozygous G/G were observed in 88.7% of cases. At that heterozygous G/A were registered in any case. In other case, among the patients, no cases of the carriage of the mutant genotypes A/A were detected. Thus, allele G and genotypes G/G of promoter gene of TNFα rs1800629 predisposed to erysipelas. Heterozygous G/A of promoter gene of TNFα rs1800629 increased the risk of erysipelas. G-allele carrier led to decrease of TNFα concentration homozygous G/G patients.

Due to quite low efficiency and high costs of in vitro fertilization protocols, there is a necessity for development of new diagnostic criteria for selection of patients. The purpose of this study was complex analysis of association of polymorphic variants of IL-1α gene (rs1800587 5`UTR region) and main diagnostic criteria of women with tubo-peritoneal infertility and success rate of in vitro fertilization procedure. We have examined 120 women with tubo-peritoneal infertility who were subjected to the microflare protocol of controlled ovarian hyperstimulation which was followed by embryo transfer. Concentration of IL-1α in blood serum was defined by ELISA method by means of test systems of the "Cytokine LLC" (St. Petersburg, Russian Federation). Polymorphic marker rs1800587 at 5`UTR region was analysed with PCR method followed by the sequencing. We have detected no particular features in distribution of polymorphic IL-1α gene variants in pregnant women. The T/T genotype seems to be a conditionally favorable predictor for pregnancy resulting from in vitro fertilization. It has been shown that the IL-1α content in blood serum of pregnant women was increased as compared to women who did not become pregnant. It was also shown that pregnant women with T/T genotype had higher serum IL-1α levels than women with other genotypes. During transvaginal puncture, we have detected that pregnant women with T/T genotype had more oocytes than women with C/C genotype. We have not found significant differences in 17-oxyprogesterone, estradiol, follicle-stimulating hormone, testosterone contents for groups of women with different IL-1α genotypes. As based on this study, the IL-1a involvement in the implantation become more evident. Further studies are required concerning influence of IL-1a on folliculogenesis, ovulation, implantation, decidualization and placenta formation.

The aim of this work was to study features of gene expression TLR2, TLR4, and TLR9 in the course of acute respiratory infection, depending on the time elapsing since the contamination, and dose of infection. The studies of in vivo models of acute respiratory infections caused by Gram-negative Klebsiella pneumoniae showed that, at infection dose of 10⁴ CFU/ml, the TLR4 gene expression levels in epithelium of upper respiratory tract at 1, 3, 10 days were increased 30 times and more, complete elimination of the pathogen was observed at 3 days. At the dose of infection of 10⁷ CFU/ml, persistence of the pathogen in upper respiratory tract was observed within a few days, accompanied by a significant increase in the level of TLR9 expression in epithelium of upper respiratory tract, and TLR4 levels in the lungs 1 day after infection, in parallel to elimination of the pathogen from the lower respiratory tract. Thus, the characteristic features of TLR4 and TLR9 gene expression in the upper respiratory tract may be considered a potential diagnostic and prognostic factors in evaluation of the course of acute respiratory infections caused by Klebsiella pneumoniae.

The aim of this work was a comparative study of the helper- (Th cells) and regulatory T cells (Treg) effects upon the phenotypic composition of B lymphocytes in blood and thyroid tissue in Graves’ disease (GD). 43 women with GD were examined. The diagnosis of GD was based on clinical and laboratory signs of the disease: complaints, clinical picture of the thyrotoxicosis with objective examination, characteristic sonographic changes in thyroid gland, as well as elevated titers of antibodies to thyroid-stimulating hormone receptor in blood serum, and corresponding changes in thyroid status. 67 practically healthy women were examined as a control. The studies of Th cells, Treg and B lymphocytes phenotypes in blood and thyroid tissue were carried out by flow cytometry using direct immunofluorescence, respectively, in whole peripheral blood and lymphocytes isolated from thyroid tissue. The relative amounts of Tregs in thyroid gland from the patients with GD corresponds to their level in the blood. We did not find any changes in the content of blood T helpers expressing vs. non-expressing CD25 receptors, as compared to the control values. In patients with GD, an increased B1 cells content was revealed in peripheral blood. The percentage of this B cell subpopulation in thyroid tissue is reduced when compared to the levels found in blood, but with increased memory B cells contents. The number of activated B lymphocytes (by CD23 marker) in blood of patients with GD is reduced when compared to control values. It was found that, in thyroid tissue, there is an even more pronounced decrease in the relative amount of activated B cells compared to the levels detected in blood from these patients. By means of correlation analysis, it was found that increase in activated B lymphocytes in blood from controls is accompanied by a co-directional reaction from Treg (the usual immunoregulatory process). In Graves’ disease, such a relationship was not found. The amounts of Treg and activated T helper cells in blood of the patients did positively correlate with common B lymphocytes, B2 cells and na ve B lymphocytes. Meanwhile, Treg’s in thyroid tissue, were completely excluded from the system of interactions with activated B lymphocytes. It is assumed that a decrease in Treg’s content in peripheral blood, along with altered functional activity is observed in patients with GD.

Periodontal disease, including gum disease, gingivitis, periodontitis and periodontal disease is frequently associated with progressive loss of bone and soft periodontal tissues. Recent studies suggest effectiveness of platelet-derived growth factor, fibroblast growth factor and other growth factors, which may stimulate regeneration of connective and bone tissue. A number of cytokines and growth factors participate in regulation of angiogenesis, but vascular endothelial growth factor (VEGF) is the most powerful agent, acting directly on the vascular endothelium. VEGF detected in saliva and endothelial cells of periodontium. VEGF plays a dominant role both in periodontal health maintenance as well as in chronic inflammatory periodontal disease. The aim of this work was to develop implementation of VEGF in periodontology, and a search for laboratory markers of therapeutic efficiency in periodontitis. We observed 19 patients aged 53-79 years with I-II grade periodontitis. In frames of periodontal therapy, the patients used a drug “Rebon. Gel for Gum” (“GF group”, Russia). The drug represents a composition of bioresorbable carbohydrates on the basis of carboxymethylcellulose, forming the cellular basis for similar extraclean matrix. It contains different sodium, potassium, phosphorus, chlorine salts in order to balance the tissue pH, and a complex of glycated recombinant polypeptides identical to cytokines and human growth factors. ELISA method was used in the biological samples for detection of VEGF, human isoform A-165 (“SCI store” Ltd., Russia), and IFNγ (JSC “Vector Best”, Russia). All our patients noted a decrease in pain after the treatment, as well as a significant acceleration of healing processes in oral cavity. Observation of the oral cavity state showed good dynamics and acceleration of bone tissue regeneration. After the treatment course, the level of IFNγ increased from 14.48 to 27.45 pg/ml. The difference before and after treatment values was significant (p = 0.022), despite a sufficient range of measured values. VEGF in gingival fluid showed a large scatter of values, from 26 to 279 pg/ml before treatment, and 16 to 198 pg/ml after treatment. Generally, a tendency for VEGF decrease was observed after treatment. To diagnose the current state of the periodontium, an importance of analyses of the gingival sulcus fluid is actual. The developed diagnostic approaches based on measuring the IFNγ, VEGF levels in screening and monitoring regimens help to provide a more effective treatment. Introduction of a complex preparation with growth factors and peptidoglycan-recognizing protein seems to accelerate epithelialization and regeneration of connective and bone tissue.