O. Kurbatova, S. Petrichuk, G. Movsisyan, Daria G. Kuptsova, T. Radygina, A. Anushenko, E. Semikina, A. Potapov
{"title":"Role of minor lymphocyte populations in development of liver fibrosis in children with glycogen storage disease","authors":"O. Kurbatova, S. Petrichuk, G. Movsisyan, Daria G. Kuptsova, T. Radygina, A. Anushenko, E. Semikina, A. Potapov","doi":"10.46235/1028-7221-10013-rom","DOIUrl":"https://doi.org/10.46235/1028-7221-10013-rom","url":null,"abstract":"Glycogen storage disease (GSD) is a rare condition that changes the way the body uses and stores glycogen. Objective: to evaluate the content of small populations of lymphocytes and their ratios in children with hepatic forms of glycogen disease depending on the stage of liver fibrosis. 148 children with GSD at the age of Me=7,7 [3,9;11,8] were examined. The comparison group consisted of 54 healthy children. The stage of liver fibrosis was carried out on the FibroScan F502 device (EchoSence, France). Immunophenotyping of lymphocytes was performed on CYTOMICS FC500 (Beckman Coulter, USA). Indicators of lymphocyte populations were analyzed as a percentage of deviation from the age norm. In children with GSD, an increase in the degree of liver fibrosis was revealed from age (R=0.57). Treg content in children with GSD was at the lower limit of the age norm and did not depend on the stage of liver fibrosis. The content of Th17 and Thact lymphocytes was significantly higher than that of the comparison group at all stages of liver fibrosis, starting from stage F1. With an increase in the stage of liver fibrosis, there was an increase in the proportion of patients with Thact and Th17 content exceeding the upper limit of the normative values (PF0-F4=0.021 and PF0-F4=0.012, respectively). An increase in Th17/Treg and Thact/Treg ratios was revealed in patients with GSD relative to the comparison group in all age groups, the dynamics of Th17/Treg and Thact/Treg ratios was characterized by their increase with age. Analysis of indicators depending on the stage of liver fibrosis in children with GSD revealed a significant increase in the Thact/Treg ratio from stage F0 to stages F1, F2, F3 and F4 (PF0-F4=0.000). The Th17/Treg index increased from stage F0 to stages F1, F2, F3 (PF0-F3=0.000). \u0000An increase in the content of Thact and Th17 lymphocytes, as well as Th17/Treg and Thact/Treg indices with an increase in the stage of liver fibrosis can be used as an additional tool in assessing fibrotic changes in the liver. Immunological indicators objectively reflect the severity of the patient's condition with hepatic forms of GSD.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89880952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of pregnancy-specific β1-glycoprotein on the expression of arginase-1 and indolamine-2,3-dioxygenase by myeloid-derived suppressor cells","authors":"V. Timganova, K. Shardina, E. Gutina","doi":"10.46235/1028-7221-10003-eot","DOIUrl":"https://doi.org/10.46235/1028-7221-10003-eot","url":null,"abstract":"Myeloid-derived suppressor cells (MDSC) - a population of immature cells of myeloid origin with inhibitory functions, mainly related to T lymphocytes. Normally, MDSC account for less than 1% of leukocytes in peripheral blood. The number of these cells increases during healthy pregnancy. However, MDSC have been shown to play a critical role in the maintenance of tumor growth and in autoimmune diseases. \u0000Because MDSC are now considered important regulators of immunity, finding ways to manipulate their functions is important for the development of therapies for malignant and autoimmune diseases, as well as for pregnancy pathologies and post-transplant complications. The immunosuppressive mechanisms of these cells are mediated by their expression of the surface molecules CD73, ADAM17, PD -L1, the enzymes arginase 1 (Arg 1), inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO), reactive oxygen species, and the production of the anti-inflammatory cytokines IL -10 and TGF-1. \u0000Pregnancy-specific 1-glycoprotein (PSG) is a pregnancy glycoprotein that has immunomodulatory effects on natural (dendritic cells and macrophages) and adaptive (T cells) immunity cells. At the same time, the effect of PSG on MDSC has not been investigated so far. Since this glycoprotein has promising pharmacological applications, it is necessary to study not only the native variant of PSG but also its recombinant form. \u0000Since the main function of MDSC is immunosuppression, the aim of our work was to evaluate one of its mechanisms, namely the intracellular expression of amino acid degradation enzymes Arg1 and IDO under the influence of native and recombinant PSG in vitro. \u0000MDSC differentiation was performed from CD11b+ cells isolated from peripheral blood of healthy volunteers. Cells were cultured for 7 days with stepwise addition of GM-CSF, IL -1, and LPS. Native (n) (1, 10, and 100 g/mL) and recombinant (r) (1 and 10 g/mL) PSG was added to the cultures three days before the end of incubation. The percentage of MDSCs (Lin- HLA-DR -CD11b+CD33+) intracellularly expressing Arg1 and IDO was determined by flow cytometry. \u0000It was found that nPSG and rPSG did not alter the amount of Arg1-expressing MDSCs at all concentrations examined. However, at a concentration of 10 g/mL, both types of proteins caused a statistically significant increase in the percentage of cells expressing IDO. \u0000We have already established that nPSG and rPSG affect MDSC differentiation by increasing the proportion of these cells belonging to the monocytic subpopulation. However, now we can say that PSG, in addition, enhances the suppressive function of the studied cells. \u0000The obtained data are novel and open perspectives for targeting myeloid suppressor cells to improve cellular technologies in science and medicine.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72636933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Dobrynina, A. Zurochka, Mariia V. Komelkova, V. Zurochka, Alexey Sarapultsev
{"title":"Disturbances in the b cell component of immune system and associated immune alterations in post-covid patients","authors":"M. Dobrynina, A. Zurochka, Mariia V. Komelkova, V. Zurochka, Alexey Sarapultsev","doi":"10.46235/1028-7221-9636-dit","DOIUrl":"https://doi.org/10.46235/1028-7221-9636-dit","url":null,"abstract":"There is only limited data on B-cell response in post-COVID patients despite its importance in studying the post-infection immunity. The present study aimed to investigate the features of the B-cell response in post-COVID patients, focusing on various B cell phenotypes. Along with the standard immunogram, the following cell phenotypes were examined: common B cells (CD45+, CD3-, CD19+); common memory cells (CD45+, CD3-, CD19+, CD27+); common non-memory cells (CD45+, CD3-, CD19+, CD5+); B1 memory cells (CD45+, CD3-, CD19+, CD5+, CD27+); B2 memory cells (CD45+, CD3-, CD19+, CD5-, CD27+); B1 non-memory cells (CD45+, CD3-, CD19+, CD5+, CD27-); and B2 non-memory cells (CD45+, CD3-, CD19+, CD5-, CD27-). The study revealed a sharp increase in B1 memory cells in 15.3% of post-COVID patients with impaired levels of B1 memory cells. This increase was accompanied by elevated levels of total B memory cells, B1 total lymphocytes (mainly, B1 memory cells), total T lymphocytes, and total IgA. By contrast, the patients with impaired B1 memory cells exhibited a sharp decrease in plasma cells, B2 lymphocytes (both memory and non-memory cells), natural killer cells, T regulatory cells, early activation T cells (CD25+), and C3a complement fragment. These findings suggest a unique immune system disorder characterized by dysregulated B lymphocyte switching from IgM to IgG and IgA synthesis, thus resulting in marked decrease in B2 lymphocyte subpopulations. This disorder may be associated with reduced T regulatory lymphocytes and early activation of T lymphocytes responsible for regulating B lymphocyte differentiation. Furthermore, the patients also exhibited reduced hemoglobin and platelet parameters, thus, potentially, contributing to hypoxia and blood clotting abnormalities. Thus, the phenotype identification of these immune system disorders in post-COVID patients requires non-standard approaches to assessing immune status, thus compicating clinical examination, but highlighting the need for immunocorrective therapies. These findings contribute to better understanding of post-COVID immune system disorders and require further investigation into the underlying causal factors.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83940419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunopharmacological aspects of studying immunotropic properties of a novel biocompound","authors":"N. А. Zabokritskiy","doi":"10.46235/1028-7221-9643-iao","DOIUrl":"https://doi.org/10.46235/1028-7221-9643-iao","url":null,"abstract":"The article presents an experimental study of immunotropic activity of a new compound, a metabiotic, based on metabolites (biologically active substances) produced by a of saprophytic Bacillus subtilis B-9909 strain, being safe for health and standardized at Russian National Collection of Industrial Microorganisms (RNCIM). The aim of our study was to experimentally evaluate the immunotropic effects of metabolites produced by the probiotic Bacillus subtilis B-9909 upon the parameters of cellular immunity tested in the animal model of induced toxic liver damage. The metabolites were isolated from the cultural liquid of Bacillus subtilis culture (RNCIM strain B-9909) during its deep cultivation in a medium containing hydrochloric acid hydrolyzate of soy flour, or pancreatic hydrolyzate of casein. At 16-18 hours of cultivation, the cells were in the exponential growth phase. The indices of cellular status were studied in experimental groups of animals, when assessing therapeutic efficacy of an experimental metabiotic sample, as compared to a group of laboratory animals treated with the reference drug (ursosan). We assessed the quantitative indicators of blood as follows: determination of phagocytic activity (FA) of peripheral blood neutrophils; measurement of metabolic activity in peripheral blood neutrophils by means of NBT-test; quantitative determination of T and B lymphocytes; the number of antibody-forming cells (AFC). Liver damage was studied in a model of acute toxic hepatitis in albino rats. Experimental toxic hepatitis was induced by 40% solution of CCl4 in vaseline oil injected intragastrically for 2 weeks at the dose of 0.2 g/kg. The results of experimental studies showed activation of phagocytic activity by peripheral blood neutrophils at the early terms of experiment, being also confirmed by the results of NBT-testing. Moreover, at the early observation terms, a significantly increased representation of T and B lymphocyte populations as well as AFC numbers, were revealed thus suggesting activation of all components of cellular immunity in response to the carbon tetrachloride toxicity. Thus, the reported studies on the cellular status of laboratory animals treated with metabolites produced by probiotic microorganisms of the genus Bacillus subtilis (B-9909) on laboratory animals with toxic liver damage allow us to conclude that the test sample of this metabiotic preparation exerts a significant immunomodulatory effect, when compared with ursosan. This evidence allows us to consider this compound a promising candidate drug for a new hepatoprotector with immunotropic effect.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78150426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Features of T cell immunity depending on the content of natural killer cells in patients with acute coronary syndrome following COVID-19","authors":"E. Safronova, L. V. Ryabova","doi":"10.46235/1028-7221-9640-fot","DOIUrl":"https://doi.org/10.46235/1028-7221-9640-fot","url":null,"abstract":"We examined 65 men with unstable angina and acute myocardial infarction (acute coronary syndrome - ACS) from 40 to 65 years old who had previously had COVID-19 and 20 people with ACS who had not undergone COVID-19. All persons also had hypertension, and they required stenting of the coronary arteries within the next 3 days after admission to the hospital. From the immunological parameters by flow cytometry on the Navios cytofluorimeter (BeckmanCoulter, USA), according to the standardized technology for assessing the lymphocytic link of immunity [1], the following were determined: ), CD45+ CD3+ CD8+ (cytotoxic T-lymphocytes), CD45+CD3-CD19+ (B-lymphocytes), CD45+CD3+CD16+CD56+ (TNK cells), CD45+CD3-CD16+CD56+ (natural killer cells), CD45+ CD3+CD4+CD25+CD127- (T-regulatory cells), CD45+ CD3+CD4+CD25+ (T-lymphocytes - early activation), CD45+CD3+HLA-DR (T-lymphocytes - late activation). All patients were divided into groups depending on the content of NK cells (natural killer cells). Patients who have had COVID-19 have 3 phenotypes of disorders (decreased NK cell count, normal and increased), while non-survivors have 2 phenotypes (decreased NK cell count and normal). The most severe condition and severity of immune disorders were found in patients who had undergone COVID-19. In patients with acute coronary syndrome and COVID-19, predominantly with normal and elevated levels of NK cells, compared with ACS patients without COVID-19, a more severe course of the disease was observed - patients with acute myocardial infarction prevailed, they had a higher mortality rate, the duration of treatment was increased, and stent thrombosis was also more common. In persons with ACS and COVID-19 with elevated NK cells, the maximum decrease in the T-cell immunity was observed: T-lymphocytes of general, T-lymphocytes-helpers, T-cytotoxic lymphocytes, T-lymphocytes of early activation, T-regulatory cells in absolute numbers compared to other groups. The lowest immunoregulatory index and, at the same time, the maximum number of T-NK-lymphocytes were observed in persons who had undergone COVID-19 and had reduced NK cells. The minimum number of T-NK lymphocytes was recorded in patients with low NK cells who did not have COVID-19. Minimal T-lymphocytes (CD45+CD3+CD4+HLA-DR+) of late activation were found in people who recovered from COVID-19 with elevated and normal NK cells. The lowest number of late activation regulatory T cells was observed in patients who did not have COVID-19, but were vaccinated, and had a normal content of NK cells. The study also allows us to more clearly define the groups of patients with ACS who need additional immunocorrection.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90730426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Kovaleva, I. Nesterova, S. N. Pikturno, G. Chudilova, L. Lomtatidze, Yu. V. Teterin, A.I. Pirogova, N. S. Prosolypova, А. M. Chulkova
{"title":"The effectiveness of immunomodulatory therapy with a synthetic analogue of the active center of the hormone thymus thymopoietin in the complex treatment of immunocompromised women with chronic infectious and inflammatory diseases of the pelvic organs","authors":"S. Kovaleva, I. Nesterova, S. N. Pikturno, G. Chudilova, L. Lomtatidze, Yu. V. Teterin, A.I. Pirogova, N. S. Prosolypova, А. M. Chulkova","doi":"10.46235/1028-7221-10011-eoi","DOIUrl":"https://doi.org/10.46235/1028-7221-10011-eoi","url":null,"abstract":"Chronic inflammatory diseases of the pelvic organs (pelvic inflammatory disease, PID) in women is among the main understudied problems in gynecology worldwide with adverse medical and socio-economic consequences, thus justifying the need for further study of immunopathogenesis and development of new approaches to treatment. Our objective was to develop new immunotherapeutic approaches to correction of combined disorders of the immune system functioning in immunocompromised women with PID and to evaluate their clinical and immunological efficacy. \u000055 women aged 20-40 years were examined, i.e., 35 patients with exacerbation of sluggish or recurrent PID, resistant to conventional therapy. Testiung was performed before complex treatment (study group 1 GI- 1) and after the course (study group 2 GI-2). Contents of T and B lymphocytes, natural killer cells (NK) (CYTOMICS FC500, USA), phagocytic and microbicidal functions of neutrophilic granulocytes (NG) were assessed in SG-1 and SG-2 before and 2-3 days after complex treatment with addition of an immunotherapeutic drug based on hexapeptide (HP) at a daily dose of 45 mg/ml intramuscularly for 10 days. \u0000In patients from SG-1, a decrease in T cells (CD3+CD19- ) and B cells (CD3-CD19+), a 2-fold increase in the content of NK CD3-CD16+CD56+ was found, along with altered functioning of NG (deficiency of actively phagocytizing NG, a decrease in their digestive function and NADPH-oxidase activity). In SG-2 patients, the treatment was followed by restoration of the T (CD3+CD19-) and B cells (CD3-CD19+), NK cells (CD3-CD16+CD56+), like as an increase in effector functions, i.e., microbial capture by NG and their killing ability due to activation of NADPH oxidases and normalization of microbicidal reserve capacity in the NG cell population. Positive clinical effect included reduction of clinical symptoms in acute period, absence of PID exacerbations over follow-up for 6 months (85.6% of cases). Occasional exacerbations of PID were associated with medical manipulations (5.7%) and unprotected sexual contacts (5.7%). \u0000The immunopathogenetically proven approach to correction of combined functional impairment of immune system in the women with PID shows a positive clinical and immunological effect.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75768779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. V. Solodovnic, T. A. Vyalova, E. V. Gabova, Pavel A. Pozdnyakov, Daria S. Bushueva
{"title":"Indicators of immunological response to non-drug therapy of chronic adenoiditis","authors":"A. V. Solodovnic, T. A. Vyalova, E. V. Gabova, Pavel A. Pozdnyakov, Daria S. Bushueva","doi":"10.46235/1028-7221-9448-ioi","DOIUrl":"https://doi.org/10.46235/1028-7221-9448-ioi","url":null,"abstract":"The aim of our work was to study individual indices of immune response in children with chronic adenoiditis and evaluate their dynamics following low-frequency ultrasonic cavitation combined with photochromotherapy included into the treatment regimen. The study involved 104 patients 3 to 15 years old, divided into three groups: the 1st control group (n = 34) received standard treatment for 7 days; 2nd group (n = 37) received a supplementary low-frequency ultrasonic cavitation irrigation of pharyngeal tonsil combined with photochromotherapy on lymphoid tissue of the pharyngeal tonsil for 7 days; the 3rd group (n = 33) received only low-frequency ultrasonic cavitation irrigation treatment. Comparative estimation of clinical and immunological indicators (sIgA, IL-1, IL-6, IL-8, IL-10, TNF) was performed prior to the therapy (day 0) and on the 7th day from the start of treatment. Before therapy, a decrease in the content of sIgA, IgA was revealed in all groups. In the second group, there was a statistically significant increase in the level of IgA after treatment, which suggests activation of local immunity factors. The dynamics of proinflammatory cytokines (IL-6, IL- 10) also indicates effectiveness of the drug treatment by reducing manifestations of the tissue immunological reactivity in pharyngeal tonsil. An increased number of anti-inflammatory IL-8 and IL- 10 cytokines could be considered a compensatory response to decreased level of proi-inflammatory cytokines. \u0000As a result, the inclusion of low-frequency ultrasonic cavitation in combination with photochromotherapy into the complex treatment for chronic adenoiditis thus stabilizing the course of immune response.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79480318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O. V. Valikova, V. Zdor, Yakov N. Tikhonov, A. Boroda, A. M. Gracheva, K. G. Kolbin
{"title":"Studies on the hormone and cytokine producing function of human cumulus cells and its interrelation with fertility in polycystic ovarian syndrome","authors":"O. V. Valikova, V. Zdor, Yakov N. Tikhonov, A. Boroda, A. M. Gracheva, K. G. Kolbin","doi":"10.46235/1028-7221-9999-sot","DOIUrl":"https://doi.org/10.46235/1028-7221-9999-sot","url":null,"abstract":"Cumulus cells (CC) are the specialized layer of follicular cells that are in close contact with the oocyte. They are considered as indirect markers of the oocyte quality. Changes of these cells suggest a damage of the ovary. Determination of cytokines in cumulus cell culture may predict the chance for the conception and development of pregnancy. The objective of the present study was to obtain a primary culture of CC from healthy donors and patients with polycystic ovarian syndrome (PCOS), to identify the most significant differences in production of key cytokines in the CC monocultures of patients and healthy individuals in order to predict the results of in vitro fertilization. Materials and methods: the cell culture technique was used, i.e., cumulus cells of healthy donors and patients with polycystic ovary syndrome were obtained by transvaginal puncture of follicles in the in vitro fertilization (IVF) program. This procedure does not affect the rights of embryo, since the CC are not used at the stage of IVF procedure and intracytoplasmic sperm injection (Ethical Committee Protocol No. 9 of May 16, 2022). IL-6, IL-10, IFN and progesteroneparameters were tested in adhesive cultures of CC by ELISA technique on days 1, 3, 7 of in vitro experiments. Results: We revealed a continuous secretion of progesterone, IL-6, IL-10, IFN in adhesive monocultures of CC. In the patients with PCOS, we have found a sharp increase of progesterone level in cultural media (p 0.01) on the 7th day, By contrast, the initially increased progesterone levels proved to be significantly decreased in donors on the 7th day of culture. Moreover, in the culture of CC from patients with PCOS (7th day of the experiment), the values of IL-6, IL-10 increased only two-fold compared with 30-fold increase of these cytokines in healthy donors (p 0.01). At the same term, we have observed a threefold decrease in IFN in the CC cultures of PCOS patients (p1-7 0.01; p 0.05) compared with cultured controls, which showed a 20-fold increase (p1-7 0.01), thus determining differences in total cytokine balance and, probably, influencing the pregnancy prognosis. Conclusion: Significant multidirectional changes of cytokine levels in the culture of cumulus cells of the patients with PCOS and in healthy individuals may be regarded as determining factors in formation of blastocyst and preservation of the embryo. A further in vitro research on the production of cytokines and sex steroids by CC is especially important on day 5 to 7, when the oocytes are selected for entry into the in vitro fertilization cycle. The study of morpho-functional properties of little-studied cumulus cells using the cell culture technique will enable us for a deeper study on the mechanisms of disturbed folliculogenesis in PCOS, and, thereby, improve the reproductive prognosis in this disorder.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73962530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Ivanova, I. N. Chaynikova, A. V. Bekpergenova, Taisiya A. Bondarenko, O. E. Chelpachenko, I. A. Zdvizhkova, N. Perunova, O. Bukharin
{"title":"Combined effect of methotrexate and bifidobacteria metabolites on TNFα AND IFNγ production by human peripheral blood mononuclears","authors":"E. Ivanova, I. N. Chaynikova, A. V. Bekpergenova, Taisiya A. Bondarenko, O. E. Chelpachenko, I. A. Zdvizhkova, N. Perunova, O. Bukharin","doi":"10.46235/1028-7221-9839-ceo","DOIUrl":"https://doi.org/10.46235/1028-7221-9839-ceo","url":null,"abstract":"Methotrexate (Mtx) is a first-line drug for the treatment of numerous rheumatic and non-rheumatic disorders, including oncological disdiseases. However, therapeutic efficacy of Mtx is limited by severe toxicity to many organs (myelo-, hepato-, nephrotoxicity, mucositis, enteritis, dysbiosis at various human biotopes, etc.). Recently, a number of studies showed that some metabolites of Bifidobacteria and Lactobacilli are able to enhance effect of chemotherapeutic drugs and limit their toxic properties. The aim of the present work was to study the possible potentiating action of Bifidobacteria cell-free supernatants and methotrexate upon secretion of pro-inflammatory TNF and IFN cytokines by human peripheral blood mononuclear cells (PBMCs). The immunoregulatory effects upon production of TNF and IFNg was evaluated in the in vitro model of cultured PBMC supplemented with Bifidobacteria metabolites, methotrexate, or their combination. Analysis of the combined effect of Bifidobacteria metabolites and Mtx on the cytokine production revealed their synergism towards the key pro-inflammatory cytokines (TNF and IFN). We found an increase against the control cultures (with Mtx only), inhibition of the early pro-inflammatory cytokine TNF production. On the contrary, we revealed an increased secretion of IFN which regulates the effector cells. The results obtained with these cytokines suggest the presence of a potentiating effect of Bifidobacteria metabolites upon anti-inflammatory and immunoregulatory properties of methotrexate. Thus, Bifidobacteria metabolites can be considered a promising agent which potentiates the therapeutic action of methotrexate by suppressing TNF secretion and stimulating IFN by immunocompetent cells. Further studies of the combined effects of Mtx and metabolites from the intestinal microbiota upon the cytokine production by effector cells could be recommended, aiming to enhance therapeutic effect of methotrexate and limit its toxic properties using the Bifidobacteria metabolites.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81636936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Nesterova, G. Chudilova, M. G. Atazhakhova, V. A. Matushkina, S. Kovaleva, V. N. Chapurina
{"title":"Quantitative and phenotypic transformation of CD16+IFNα/βR1-CD119+, CD16+IFNα/βR1+CD119- and CD16+IFNα/βR1+CD119+ neutrophil granulocytes subsets in patients with post-COVID syndrome","authors":"I. Nesterova, G. Chudilova, M. G. Atazhakhova, V. A. Matushkina, S. Kovaleva, V. N. Chapurina","doi":"10.46235/1028-7221-9994-qap","DOIUrl":"https://doi.org/10.46235/1028-7221-9994-qap","url":null,"abstract":"In patients who underwent COVID-19, various manifestations of post-COVID syndrome (PCS) are noted, causing the development of disorders accompanying severe viral infections, complicated by chronic fatigue syndrome (CFS) and severe cognitive disorders (CD). Studying the molecular mechanisms of these disorders in the system of neutrophilic granulocytes (NG) in patients with PCS associated with IFN production, receptor function of NG, in particular, their subsets expressing IFN/R, IFNR(CD119), is relevant for the search for therapeutic strategies, restoration and enhancement of the innate immune response after COVID-19. \u0000Our objective was to clarify the quantitative and phenotypic characteristics of certain subsets of neutrophil granulocytes, i.e., CD16+IFN/R1-CD119+, CD16+IFN/R1+CD119-, CD16+IFN/R1+CD119+, in peripheral blood of patients with post-COVID syndrome. \u0000We have examined 39 patients (24-60 years old) with PCS 3 months after COVID-19 (study group 1, SG1). The comparison group (CG) included 30 volunteers examined over the pre-COVID period. Detection of herpesvirus infections (HSV1, EBV, HHV6, CMV) was carried out in scrapings from the tonsils and the posterior wall of the pharynx. To determine the severity of the clinical PCS symptoms, a questionnaire was used to assess its severity using a point scale. The content and phenotype of NG subsets CD16+IFN/R1-CD119+, CD16+IFN/R1+CD119-, CD16+IFN/R1+CD119+ were assessed by means of FC 500 (Beckman Coulter, USA). \u0000In all patients of SG1, clinical manifestations of CFS and CD were revealed, at the average severity rates of 16.0 points (14.75-20.25). When detecting herpesvirus infections, 37.2% had only HSV1 infection; 62.8% of patients showed mixed infection (HSV1, EBV, HHV6), which exhibited more pronounced clinical symptoms. We have noted absence of CD16+IFN/R1+CD119+NG subset and phenotype transformation of CD16+IFN/R1-CD119+NG, CD16+IFN/R1+CD119-NG subsets. Increased density expression of CD16, IFN/R1, CD119 receptors was also found (p1-3 0.05) thus suggesting ability to accept the interferon signaling and response. \u0000Reduced infectious burden in the post-COVID period and adequate functioning of the immune system, including the neuroimmunoendocrine regulation mechanisms, should contribute to the functional recovery of various organs, systems, thus neutralizing the PCS manifestations. Therefore, usage of recIFN2b in combination with highly active antioxidants may contribute to development of protective immunity, prevention of acute respiratory viral infections, exacerbation of chronic infections, and restoration of the NG phenotypes followed by restoration of anti-infectious immune balance.","PeriodicalId":21524,"journal":{"name":"Russian Journal of Immunology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77223485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}