Cytokine Production In Patients Research Articles

Altered Body Composition and Cytokine Production in Patients with Elevated HOMA-IR after SARS-CoV-2 Infection: A 12-Month Longitudinal Study.

Altered body composition and cytokine production due to SARS-CoV-2 antigens may affect homeostasis model assessment for insulin resistance (HOMA-IR) after SARS-CoV-2 infection. To elucidate this phenomenon, we conducted a longitudinal study involving 47 COVID-19 patients, who were followed up for 12 months. During recruitment, body composition and glucose indices were measured, and heparin blood samples were collected for measuring cytokine production. HOMA-IR was considered an elevated or non-elevated group based on the ratio between HOMA-IR at 12 months and 1 month of convalescence. Those with elevated HOMA-IR had a significantly higher body mass index, body fat percentage, and visceral fat rating and had a lower lean mass and lean/fat mass ratio than their counterparts. During the convalescent period, the elevated HOMA-IR group had lower TNFα, IFNγ, IL-2, IL-10, and granzyme B expression levels but had higher TNFα/IL-10, IFNγ/IL-10, IL-2/IL-10, and granzyme B/IL-10 ratios than the other group. The reduced cytokine production and pro-/anti-inflammatory imbalance in patients with elevated HOMA-IR may suggest immune cell dysfunction toward SARS-CoV-2. Patients with elevated HOMA-IR after SARS-CoV-2 infection may experience an increase in BMI and body fat percentage, leading to increased immune dysfunction and chronic inflammatory condition. A nutritional approach and promotion of physical activity may help reduce HOMA-IR and ameliorate glucose indices in these patients.

4-Octyl itaconate inhibits inflammation via the NLRP3 pathway in neuromyelitis optica spectrum disorders.

Neuromyelitis optica spectrum disorders (NMOSD) are rare inflammatory astrocytic diseases of the central nervous system (CNS). The roles of immune response gene-1 (IRG1) and the IRG1-itaconic acid-NLRP3 inflammatory pathway in the pathogenesis of NMOSD and the effects of 4-octyl itaconate (4-OI) on the NLRP3 inflammatory pathway in NMOSD are unclear. This study aimed to determine the role of IRG1 and the activation status of the NLRP3 inflammatory pathway in acute-onset NMOSD and to investigate the inhibitory effects of 4-OI on NLRP3 inflammasome activation via the IRG1-itaconic acid-NLRP3 pathway in monocytes and macrophages by using in vitro models. Peripheral blood mononuclear cells (PBMCs) and serum were collected from patients with acute NMOSDs and healthy controls (HC), followed by monocyte typing and detection of the expression of NLRP3-related inflammatory factors. Subsequently, the effects of 4-OI on the IRG1-itaconic acid-NLRP3 pathway were investigated in peripheral monocytes from patients with NMOSD and in macrophages induced by human myeloid leukemia mononuclear cells (THP-1 cells) via in vitro experiments. Patients with acute NMOSD exhibited upregulated IRG1 expression. In particular, the upregulation of the expression of the NLRP3 inflammasome and proinflammatory factors was notable in monocytes in acute NMOSD patients. 4-OI inhibited the activation of the IRG1-itaconic acid-NLRP3 inflammatory pathway in the PBMCs of patients with NMOSD. 4-OI could effectively inhibit NLRP3 signaling, leading to the inhibition of proinflammatory cytokine production in patients with NMOSD-derived PBMCs and in a human macrophage model. Thus, 4-OI and itaconate could have important therapeutic value for the treatment of NMOSD in the future.

Features of cytokine production at the systemic and local level in patients of reproductive age with external genital endometriosis

Objective: to establish the features of cytokine production in patients of reproductive age with external genital endometriosis at various stages of the disease.Materials and methods: the study included 52 patients with external genital endometriosis (EGE). Group I consisted of 31 patients with stages I–II of EGE, group II — 21 patients with stages III–IV of the disease, control group — 20 women without endometriosis. Serum samples were obtained before anesthesia, and peritoneal fluid (PF) samples were obtained during endoscopic examination of patients. Determination of the content of cytokines in blood serum and peritoneal fluid was carried out by enzyme immunoassay using a multifunctional counter for enzyme immunoassays with Victor software (Finland). TNF-α, IL-10 — using reagents from BenderMed Systems (Austria). IL-13, IL-18 using reagents from Cloud-CloneCorp (USA) according to the manufacturer’s recommendations. Application software packages (Megastat and Statistica 10.0) were used to create a database and conduct statistical research. To determine statistical differences between groups, the Mann-Whitney test was used for independent groups and the Wilcoxon test for dependent groups. P values less than 0.05 were considered statistically significant. Data are presented as median and quartiles.Results: at stages I–II of EGE, an increase in the level of TNF-α, IL-18 was detected in the blood serum and peritoneal fluid, which can stimulate proliferation, invasion of endometrial cells and neovascularization; stage III–IV of the disease was characterized by an increase in the level of TNF-α, IL-10, IL-13 in the peritoneal fluid, which promotes disease progression by evading ectopic endometrial cells from immune control.Conclusion: the identified features of the production of pro- and anti-inflammatory cytokines at the systemic and local level at various stages of EGE confirm their importance in the development of the disease. Further research is needed to understand the mechanisms underlying the progression of NGE and to develop methods for early diagnosis.

Mesenchymal stem cells modulate IL-17 and IL-9 production induced by Th17-inducing cytokine conditions in autoimmune arthritis: an explorative analysis

BackgroundThe importance of proinflammatory T-cells and their cytokine production in patients with autoimmune arthritis has been widely described. Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have come into focus as a potential therapeutic concept. The aim of this study was to investigate the influence of MSCs on the phenotype, cytokine profile, and functionality of naive and non-naive CD4+ T-cells from healthy donors (HD) and patients with autoimmune arthritis under Th17-cytokine polarizing conditions in an explorative way using a transwell system prohibiting any cell–cell-contact.MethodsMagnetically isolated naive and non-naive CD4+ T-cells were stimulated under Th17-polarizing proinflammatory cytokine conditions in presence and absence of bone marrow derived mesenchymal stromal cells (MSCs). After an incubation period of 6 days, the proportions of the T-cell subpopulations TEMRA (CD45RA+CD27−), memory (CD45RA−CD27+), effector (CD45RA−CD27−) and naive cells (CD45RA+CD27+) were determined. Quantitative immunofluorescence intensity was used as a measure for IL-9, IL-17 and IFN-γ production in each subpopulation.ResultsIn isolated naive CD4+ T-cells from HD and patients, MSCs suppressed the differentiation of naive towards an effector phenotype while memory and naive cells showed higher percentages in culture with MSCs. In patients, MSCs significantly decreased the proportion of IL-9 and IL-17 producing effector T-cells. MSCs also reduced IFN-γ production in the naive and memory phenotype from HD.ConclusionThe results of the study indicate significant immunomodulatory properties of MSCs, as under Th17-polarizing conditions MSCs are still able to control T-cell differentiation and proinflammatory cytokine production in both HD and patients with autoimmune arthritis.

Assessment of interleukin-10 promoter variant (-1082A/G) and cytokine production in patients with hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) is a condition that results in acute kidney failure mainly in children, which is caused by Shiga toxin-producing Escherichia coli and inflammatory response. Although anti-inflammatory mechanisms are triggered, studies on the implication in HUS are scarce. Interleukin-10 (IL-10) regulates inflammation in vivo, and the interindividual differences in its expression are related to genetic variants. Notably, the single nucleotide polymorphism (SNP) rs1800896 -1082 (A/G), located in the IL-10 promoter, regulates cytokine expression. Plasma and peripheral blood mononuclear cells (PBMC) were collected from healthy children and HUS patients exhibiting hemolytic anemia, thrombocytopenia, and kidney damage. Monocytes identified as CD14+ cells were analyzed within PBMC by flow cytometry. IL-10 levels were quantified by ELISA, and SNP -1082 (A/G) was analyzed by allele-specific PCR. Circulating IL-10 levels were increased in HUS patients, but PBMC from these patients exhibited a lower capacity to secrete this cytokine compared with those from healthy children. Interestingly, there was a negative association between the circulating levels of IL-10 and inflammatory cytokine IL-8. We observed that circulating IL-10 levels were threefold higher in HUS patients with -1082G allele in comparison to AA genotype. Moreover, there was relative enrichment of GG/AG genotypes in HUS patients with severe kidney failure. Our results suggest a possible contribution of SNP -1082 (A/G) to the severity of kidney failure in HUS patients that should be further evaluated in a larger cohort.

Deciphering prognostic value of CD22 and its contribution to suppression of proinflammatory cytokines production in patients with IgA nephropathy

BackgroundCD22, mainly expressed in mature B cells, could negatively regulate the function of B cells by binding to sialic acid-positive IgG (SA-IgG). Soluble CD22 (sCD22) is generated by the cleavage of the extracellular domain of CD22 on the membrane surface. However, the role of CD22 in IgA nephropathy (IgAN) remains unknown. MethodsA total of 170 IgAN patients with a mean follow-up of 18 months were included in this study. The sCD22, TGF-β, IL-6 and TNF-α were detected using commercial ELISA kits. SA-IgG were purified to stimulate peripheral blood mononuclear cells (PBMCs) from IgAN patients. ResultsThe plasma levels of sCD22 were lower in IgAN patients in comparison with healthy control. Furthermore, CD22 mRNA levels in PBMCs from patients with IgAN were significantly lower than those of healthy controls. The plasma levels of sCD22 were positively correlated to the mRNA levels of CD22. We found that patients with higher sCD22 levels had a lower level of serum creatinine and a higher level of eGFR on the time of renal biopsy and a higher remission rate of proteinuria and a lower risk of kidney events at the end of follow-up. The logistic regression analysis showed sCD22 was associated with an increased odd of proteinuria remission after being adjusted for eGFR, proteinuria, and SBP. After adjusting for confounding variables, sCD22 was a borderline significant predictor of less kidney composite endpoint. In addition, the sCD22 levels were positively associated with SA-IgG in plasma. The experimental results in vitro showed that addition of SA-IgG enhanced the release of sCD22 in cell supernatant and the phosphorylation of CD22 in PBMCs, further inhibiting the production of IL-6, TNF-α, and TGF-β in cell supernatant in a dose-dependent manner. Pretreatment with CD22-antibody significantly increased the expression of cytokines in PBMCs. ConclusionsThis is the first study to demonstrate that lower plasma soluble CD22 in IgAN patients and high soluble CD22 levels are associated with an increased odd of proteinuria remission and a decreased odd of kidney endpoint. The interaction between CD22 and SA-IgG can inhibit proliferation and inflammation release in PBMCs from IgAN patients.

COVID-19 plasma exosomes promote proinflammatory immune responses in peripheral blood mononuclear cells

Elevated serum cytokine production in COVID-19 patients is associated with disease progression and severity. However, the stimuli that initiate cytokine production in patients remain to be fully revealed. Virus-infected cells release virus-associated exosomes, extracellular vesicles of endocytic origin, into the blood to deliver viral cargoes able to regulate immune responses. Here, we report that plasma exosomes of COVID-19 patients contain SARS-CoV-2 double stranded RNA (dsRNA) and stimulate robust production of interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and other inflammatory cytokines and chemokines by human peripheral mononuclear cells. Exosome depletion abolished these stimulated responses. COVID-19 plasma exosomes induced proinflammatory responses in CD4+ T cells, CD8+ T cells, and CD14+ monocytes but not significantly in regulatory T cells, Th17 T cells, or central memory T cells. COVID-19 plasma exosomes protect the SARS-CoV-2 dsRNA cargo from RNase and deliver the dsRNA into recipient cells. These exosomes significantly increase expression of endosomal toll-like receptor 3 (TLR3), TLR7, TLR8, and TLR9 in peripheral T cells and monocytes. A pharmacological inhibitor of TLR3 considerably reduced cytokine and chemokine production by CD4+ and CD8+ T cells but not by CD14+ monocytes, highlighting divergent signaling pathways of immune cells in response to COVID-19 plasma exosomes. Our results identify a novel model of intercellular crosstalk following SARS-CoV-2 infection that evoke immune responses positioned to contribute to elevated cytokine production associated with COVID-19 progression, severity, and long-haul symptoms.

IL-6 production through repression of UBASH3A gene via epigenetic dysregulation of super-enhancer in CD4+ T cells in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is associated with immune dysfunction. UBASH3A as a negative regulator of T cell receptors (TCRs) signaling is a susceptible factor in RA. The aim of this study was to determine the role of UBASH3A in RA pathogenesis, by assessing the role of super-enhancer (SE) in the control of UBASH3A expression in CD4+ T cells and the contribution of the latter in proinflammatory cytokine production in patients with RA.MethodsUBASH3A mRNA and protein levels were quantified by PCR and western blotting, respectively. The cells were treated with a locked nucleic acid to inhibit enhancer RNA (eRNA) expression. Chromatin immunoprecipitation was used to identify the factors recruited to UBASH3A loci displaying SE architecture. CD4+ T cells were transfected with UBASH3A plasmids, and cytokine levels were measured by a cytometric bead array.ResultsUBASH3A was extracted as a RA susceptibility gene associated with SNPs in the SEs that are highly expressed in CD4+ T cells by in silico screening. UBASH3A mRNA and protein expression levels were lower in CD4+ T cells of RA patients than in the control. eRNA_1 and eRNA_3 knockdown reduced UBASH3A mRNA levels. RA patients exhibited accumulation of BTB and CNC homology 2 (BACH2), the silencing transcription factor, at the UBASH3A loci in CD4+ T cells, but not the SE-defining factor, mediator complex subunit 1 (MED1)/bromodomain 4 (BRD4). However, opposite changes were observed in the control. Stimulation of TCRs expressed on CD4+ T cells of RA patients resulted in interleukin (IL)-6 production, while UBASH3A over-expression significantly inhibited the production.ConclusionsIn RA, transcription of UBASH3A is suppressed via epigenetic regulation of SE in CD4+ T cells. Low UBASH3A levels result in excessive TCR signal activation with subsequent enhancement of IL-6 production.

Decreased Interleukin-1 Family Cytokine Production in Patients with Nontuberculous Mycobacterial Lung Disease.

Nontuberculous mycobacteria (NTM) cause pulmonary disease in individuals without obvious immunodeficiency. This study was initiated to gain insight into the immunological factors that predispose persons to NTM pulmonary disease (NTMPD). Blood was obtained from 15 pairs of NTMPD patients and their healthy household contacts. Peripheral blood mononuclear cells (PBMCs) were stimulated with the Mycobacterium avium complex (MAC). A total of 34 cytokines and chemokines were evaluated in plasma and PBMC culture supernatants using multiplex immunoassays, and gene expression in the PBMCs was determined using real-time PCR. PBMCs from NTMPD patients produced significantly less interleukin-1β (IL-1β), IL-18, IL-1α, and IL-10 than PBMCs from their healthy household contacts in response to MAC. Although plasma RANTES levels were high in NTMPD patients, they had no effect on IL-1β production by macrophages infected with MAC. Toll-like receptor 2 (TLR2) and TWIK2 (a two-pore domain K+ channel) were impaired in response to MAC in PBMCs of NTMPD patients. A TLR2 inhibitor decreased all four cytokines, whereas a two-pore domain K+ channel inhibitor decreased the production of IL-1β, IL-18, and IL-1α, but not IL-10, by MAC-stimulated PBMCs and monocytes. The ratio of monocytes was reduced in whole blood of NTMPD patients compared with that of healthy household contacts. A reduced monocyte ratio might contribute to the attenuated production of IL-1 family cytokines by PBMCs of NTMPD patients in response to MAC stimulations. Collectively, our findings suggest that the attenuated IL-1 response may increase susceptibility to NTM pulmonary infection through multiple factors, including impaired expression of the TLR2 and TWIK2 and reduced monocyte ratio. IMPORTANCE Upon MAC stimulation, the production of IL-1 family cytokines and IL-10 by PBMCs of NTMPD patients was attenuated compared with that of healthy household contacts. Upon MAC stimulation, the expression of TLR2 and TWIK2 (one of the two-pore domain K+ channels) was attenuated in PBMCs of NTMPD patients compared with that of healthy household contacts. The production of IL-1 family cytokines by MAC-stimulated PBMCs and MAC-infected monocytes of healthy donors was reduced by a TLR2 inhibitor and two-pore domain K+ channel inhibitor. The ratio of monocytes was reduced in whole blood of NTMPD patients compared with that of healthy household contacts. Collectively, our data suggest that defects in the expression of TLR2 and TWIK2 in human PBMCs or monocytes and reduced monocyte ratio are involved in the reduced production of IL-1 family cytokines, and it may increase susceptibility to NTM pulmonary infection.

Metal hypersensitivity and pro-inflammatory cytokine production in patients with failed orthopedic implants: A case-control study

Orthopedic implants heal well without complications in most patients but fail for unclear reasons in some individuals. This study determined the relevance of metal hypersensitivity in patients with failed orthopedic implants and those requiring orthopedic implant surgery. The study included 35 patients with failed orthopedic implants and 15 subjects scheduled for orthopedic implant surgery. The production of selected pro-inflammatory cytokines was measured in patients with failed orthopedic implants. Metal hypersensitivity was measured in all subjects using the MELISA® test. Of common metals in orthopedic alloys, the patients with failed orthopedic implants responded most frequently to nickel, chromium, titanium, iron, and molybdenum. Hypersensitivity to metals found in implants was measured in 40% of patients with failed implants. The study also showed that titanium exposure in patients with titanium hypersensitivity might lead to implant failure. Metal hypersensitivity testing should be offered to patients before surgery to minimize the risk of implant failure.

Regulatory T Cells Decreased during Recovery from Mild COVID-19.

Depending on the intensity and duration of SARS-CoV-2 infection, the host immune response plays a significant role in immunological protection. Here, we studied the regulatory T-cell (Treg) response in relation to kinetic change and cytokine production in patients with mild COVID-19. Nineteen SARS-CoV-2-positive patients were recruited, and blood was collected at four time points, i.e., seven days after admission, after discharge, and one and three months after recovery. CD3+CD4+CD25+CD127low was marked as the Treg population, with IL-10 and TGF-β used to study cytokine-producing Tregs. IFN-γ-producing CD8+ T cells were observed for an effector response. The Treg percentage in patients with mild COVID-19 increased during hospitalization compared to during the recovery period. Peripheral blood mononuclear cells (PBMCs) were quantified, and the T-cell response was characterized by re-stimulation with S1 and N peptides. IL-10 and TGF-β were produced by CD25+CD127low T cells during the active infection phase, especially with N peptide stimulation. Compared to N peptide stimulation, S1 peptide stimulation provided superior IFN-γ-secreting CD8+ T-cell responses. Our results suggest that while IFN-γ+CD8+ T cells confer antiviral immunity, cytokine-producing Tregs may have a substantial role in regulating inflammatory responses in mild SARS-CoV-2 infection. Novel vaccine development may also consider enhancing T-cell repertoires.

Cell activation, PD-1 expression and in vitro cytokine production in patients with juvenile systemic lupus erythematosus.

Juvenile systemic lupus erythematosus (jSLE) is known to be more severe and with a higher frequency of renal and central nervous system impairment when compared to systemic lupus erythematosus in adults. The study of immunological characteristics of jSLE patients might help to envisage better treatment strategies to reduce the burden of the disease. To characterize peripheral lymphocytes, assessing activation markers, and PD-1 expression on T cells; to evaluate in vitro cytokine expression upon stimulation in jSLE patients and age-matched controls. Eighteen jSLE patients on low disease activity and 25 matched healthy adolescents were evaluated for immune activation and PD-1 expression on peripheral blood lymphocytes by flow cytometry. Twenty-one cytokines were assessed by X-MAP technology after in vitro stimulation of peripheral blood with phytohemagglutinin. jSLE patients had lower numbers of CD4 T, CD8 T, B, and NK cells; higher central memory CD8 T cell percentages were noted in jSLE adolescents in comparison with controls (p = 0.014). B cells subsets showed a higher percentage of exhausted memory subset than controls (p = 0.014). The expression of PD-1 on CD4 T and CD8 T cells did not show relevant changes in jSLE adolescents. After stimulation of peripheral blood, cell supernatant of jSLE patients showed a trend to lower concentrations of IL-10 (p=0.080) and higher concentrations of IL-23 (p = 0.063) than controls. jSLE patients on low disease activity maintain lymphopenia of all subsets, with a B cell profile of exhaustion. Upon in vitro stimulation, peripheral blood cell supernatant showed a shift to IL-23, suggesting a role of inhibitors of this cytokine as another potential therapeutic target for those patients.

Seasonal Variations in the Concentration of Particulate Matter in the Air of Cracow Affect the Magnitude of CD4+ T Cell Subsets Cytokine Production in Patients with Inflammatory and Autoimmune Disorders

Recently, the increased prevalence of chronic civilization diseases triggered by environmental pollution has been observed. In this context, the role of air pollution in the pathogenesis of autoimmune and/or inflammatory disorders is poorly elucidated. Here, we asked whether seasonal changes in the air quality of the city of Cracow affect the polarization of T cell subsets in healthy donors (HD) and patients with rheumatoid arthritis (RA), multiple sclerosis (MS), and atherosclerosis (AS). Peripheral blood mononuclear cells (PBMCs) from HD and patients were exposed in vitro to particulate matter isolated from the air of Cracow (PM CRC). Blood samples were collected in two seasons (winter and summer), with differences in air concentration of particulate matter of 10 μm (PM10) (below or above a daily limit of 50 µg/m3). The obtained data showed a significantly elevated frequency of CD4+ lymphocytes specific for IFN-γ and IL-17A after the exposure of PBMCs to PM CRC. This was observed for all patients’ groups and HD. In the case of patients, this effect was dependent on the seasonal concentration of PM in the air, paradoxically being less pronounced in the season with a higher concentration of air pollution. These observations may suggest the role of air pollution on the course of inflammatory and autoimmune disorders.

Imbalance of NK cell subpopulations and polymorphisms of proinflammatory cytokine genes in the pathogenesis of atherosclerosis

Understanding the pathogenetic mechanism of development and identifying trigger markers of the disease will significantly increase the efficiency of pre-nosological diagnosis and medical follow-up of patients. In this case, one should take into account the role of mutations in cytokine genes, which affect their biochemical activity and production level. The objective of the study was to investigate the role of mediators of acute and chronic inflammation (IL-17A, IL-1â, TNFá and IL-4), the ratio of natural killer cell subpopulations (CD56hiCD16-/CD56loCD16+) in pathogenesis of coronary atherosclerosis resulting into coronary heart disease.To analyze the results, an integrated approach was used, including molecular genetic methods such as polymerase chain reaction, typing of single-nucleotide substitutions in cytokine genes, isolation and cultivation of peripheral blood mononuclear cells, assessment of spontaneous and in vitro-induced production of immune system mediators, enzyme-linked immunosorbent assay, cytotoxic test, flow cytometry with monoclonal antibodies (Beckman Coulter, USA) to CD16, CD56 NK markers.The study included 130 residents of the North Caucasus, including the patients (n = 62) treated at the Cardiology Department of the Adyghe Republican Clinical Hospital (ARCB) with a verified diagnosis of ischemic heart disease (IHD), and a control group (n = 68), represented by unrelated healthy donors.Overexpression of cytokines in IHD patients was associated with distinct single nucleotide substitutions in certain genes. Studying a group of residents from the Republic of Adygeya, the authors experimentally established that harboring the 511C allele of the IL-1â gene (p < 0.0004; OR = 4.67), A197A of the IL-17A gene genotype (p < 0.04; OR = 3.88), G308 SNP of TNFá gene (p < 0.01; OR = 3.41), and 589T variant of IL-4 gene (p < 0.04; OR = 2.45) are associated with hyperproduction of the first-wave inflammatory mediators that increase the risk of developing ischemic heart disease. In atherosclerosis and associated cardiovascular diseases, we have noted a significant decrease in spontaneous and induced activity of natural killer cells involved in the utilization of “foamy cells”. The NK activity of peripheral blood mononuclear cell in patients with coronary heart disease is significantly reduced. In the IHD patients, an imbalance of phenotypically and functionally different CD56hiCD16-/CD56loCD16+ NK subpopulations with a predominance of CD56hiCD16- phenotype were revealed. Conclusions: Immuno-inflammatory mechanisms of evolving coronary atherosclerosis are associated with single-nucleotide substitutions, i.e., polymorphisms in the promoter regions of the IL-17A (G197A), IL-1 â (T511C), and TNFá (G308A), the known mediators of acute and chronic inflammation.Genetically determined overexpression of IL-17A, IL-1â, and TNFá, confirmed in experiments on evaluation of spontaneous and stimulated cytokine production in patients with CHD, together with reduced NK activity of РВМС, due to predominance of CD56hiCD16-, a subpopulation with high cytokine production, manifested by an increased pro-inflammatory component that triggers and provides long-term support to pathophysiological processes of atherosclerosis.

Features of innate and adaptive immunity in patients with Parkinson's disease

Introduction. T cells play a significant role in neuroinflammation in Parkinson's disease (PD). Gamma delta T cells are an under-researched 'minor' subpopulation of T cells. An assessment of the immune system in patients with PD, with a focus on Т cells, provides new data on the pathogenesis of neurodegenerative diseases. The aim of the study was to examine the lymphocyte subpopulations, nonclassical Т cells, as well as cytokine production in patients with 3 stage PD complicated by motor fluctuations. Materials and methods. We examined 20 patients with 3 stage PD receiving dopaminergic combination therapy (main group) and 20 age-matched patients with chronic cerebrovascular disease (comparison group). Considering the suspected role of chronic constipation in maintaining dysbiosis and chronic inflammation in patients with PD, the presence of constipation was an inclusion criterion for this study. The subpopulation profile of the peripheral blood lymphocytes was assessed using flow cytofluorometry, as well as cytokine levels using enzyme linked immunosorbent assay. Results. It was found that the number of mature CD3+ T cells with or chains as the T-cell receptors (TCR) in the lymphocyte population was significantly lower in patients with PD median 74% (57.383.5)) than in the comparison group (median 80% (73.086.0); р = 0.014. There was also a statistically significant reduction in the number of CD3+CD56+ natural killer (NK) T cells in the group of patients with PD vs. the comparison group 4.7% (1.37.7) vs. 7.8% (0.824); р = 0.036. At the same time, the number of CD3CD56+ NK cells was significantly higher in the group of patients with PD (16.4% (934)) vs. the comparison group 8.7% (515); р = 0.001. Moreover, the main group had a statistically significantly higher number of activated CD3CD8+ NK cells 7% (4.513.5) vs. the comparison group 3.5% (0.864.9); р 0.001. Out of the total number of Т cells, the TCR CD4+CD8 subpopulation was statistically smaller in the group of patients with PD 13.6% (6.227.0) than in the comparison group 29.8% (4.052.1); р = 0.016. The study of cytokine levels in the group of patients with PD showed a significant increase in the induced production of interleukin-1 (IL-1), as well as a high (aberrant) spontaneous production of IL-10, which was 227.5 pg/ml in patients with PD when the normal range is 023 pg/ml. The correlation analysis showed that the TCR CD4+CD8 subpopulation and cytokines in the group of patients with PD had a statistically significant (p = 0.048) negative correlation with the induced production of IL-10 (r = 0.745) and a significant (p = 0.042) positive correlation with the induced production of the pro-inflammatory cytokine IL-1 (r = 0.648). There was a trend towards increased spontaneous production of IL-10 (r = 0.602; p = 0.0506) as the level of the TCR CD4+CD8 T helper cells decreased. Conclusion. Changes were found in the blood of patients with PD, which indicate a chronic inflammatory process: increased number of CD3CD56+ NK cells, including activated CD3CD8+ cells, and increased production of pro-inflammatory cytokine IL-1 and anti-inflammatory cytokine IL-10. A decrease was found in the level of a minor subpopulation of T cells, TCR CD4+CD8. The correlation found between this subpopulation and the production of pro- and anti-inflammatory cytokines indicates its role in regulation of chronic inflammation in PD.

Local cytokine production in patients with external genital endometriosis

The article presents the results of the investigation of cytokine production by endometrioid heterotopias in organotypic cultivation in comparison with the cell secretory activity of peritoneal fluid and endometrial tissue in women with external genital endometriosis.
 The obtained results show systemic changes of regulation of cytokine production in the process of external genital endometriosis development.

Novel Mechanisms of Innate Immune System Regulation Following SARS-CoV-2 Exposure

Abstract The SARS-CoV-2 pandemic has wreaked havoc on our public health system and economy. The outcome of SARS-CoV-2 infection is determined by host-virus interactions and anti-viral immune responses. A delicate balance must be struck between mounting a vigorous immune response to eradicate the virus and quelling overactive inflammation to protect the host. Indeed, overzealous inflammation is associated with the “cytokine storm” reported in an alarming number of COVID-19 patients and underlies the Multisystem Inflammatory Syndrome reported in pediatric cases. Initial studies have suggested that SARS-CoV-2 is capable of inhibiting type-I interferon signaling, hijacking cell death processes, and inducing robust pro-inflammatory cytokine production in patients with poor outcomes. Here, we confirm many of these previous findings using whole genome transcriptomics approaches in human patients and complementary mechanistic studies using SARS-CoV-2 infection in K18-hACE2 mice. Using these approaches, we further identify 12 critical cytokines that appear to be associated with the overzealous immune response in COVID-19 patients. Further studies and pathway analysis identified members of the NBD-LRR (NLR) family of pattern recognition receptors that regulate distinct mechanisms underlying overzealous inflammation. Together, these data provide insight into novel mechanisms of immune system regulation that appear responsible for modulating several aspects of SARS-CoV-2 pathobiology.

Systemic cytokine production in patients with bronchial asthma depending on the clinical-pathogenetic phenotype of the disease

Systemic cytokine production in patients with bronchial asthma depending on the clinical-pathogenetic phenotype of the disease

Features of proinflammatory cytokine production in patients with allergic rhinitis combined with <i>Helicobacter pylori</i>-associated pathologies

Investigating a role for pro- and anti-inflammatory cytokines in immune and inflammatory response represents one of the most pressing topics in current immunology. There have been accumulated a great body of data regarding the cytokine status during inflammatory processes in gastrointestinal tract. However, many issues remain poorly elucidated. Moreover, most of the studies were mainly aimed at examining biopsy material cytokines collected from various parts of the gastrointestinal tract or gastric juice. Here we present the data on investigating the features of cytokine production in patients with allergic rhinitis combined with H. pylori-associated diseases of the upper gastrointestinal tract. A total of 225 patients aged 18 to 40 years (mean age 29.5±6.74 years) were examined, among which 43 patients suffered from allergic rhinitis, 66 patients had inflammatory diseases of the upper gastrointestinal tract (chronic gastritis/gastroduodenitis), and 69 patients — allergic rhinitis with concomitant inflammatory diseases of the upper gastrointestinal tract. Patients were stratified to various study groups depending on diagnosed allergic rhinitis and H. pylori infection. Serum IL-6 and IL-8 level and complete blood cell count were measured. Statistical significance for difference in parameter frequencies between independent groups was assessed by using Fisher's exact test or χ2 criteria. It was shown that serum IL-6 level in H. pylori-negative patients was within the reference interval with single spikes, whereas its production was markedly increased in patients with H. pylori infection regardless of allergic pathology. Frequency of subjects with elevated serum IL-8 level was comparable between groups of patients with gastrointestinal diseases, but significantly higher than that one in the control group. An interdependence between serum IL-8 level and white blood cell count was found, which is of interest for predicting development of the inflammatory process. Thus, the serum IL-8 level during the upper gastrointestinal tract inflammatory diseases was increased regardless of verified of H. pylori infection and allergic rhinitis, whereas increased IL-6 serum level was observed solely in H. pylori-positive patients.

Cytokine production in patients with recurrent acute tonsillitis: analysis of tonsil samples and blood

The aim of this study was to examine T cell function in tonsils of patients with recurrent acute tonsillitis (RAT) or peritonsillar abscess (PTA) by analyzing the cytokine production following T cell receptor (TCR) and co-receptor stimulation with a combination of anti-CD3 and anti-CD28 antibodies. The release of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A from isolated, stimulated T cells of 27 palatine tonsils (10 RAT, 7 PTA, 10 tonsils without inflammation) was measured via a bead-based flow cytometric analysis. The results were compared with the cytokine release of isolated peripheral T cells in a subset of the same patients (6 PTA, 4 patients without signs of inflammation in the blood). TCR stimulation increased the concentration of released cytokines in tonsil and blood as well as in different forms of inflammation and tissue with no inflammation. Stimulation increased the pro-inflammatory cytokines TNF-α, IFN-γ, and IL-2 more than the anti-inflammatory cytokines IL-4 and IL-10 in tonsil and blood samples in RAT, PTA, and samples without inflammation. Blood of patients with PTA showed a higher pro-inflammatory cytokine level compared to the samples of patients without inflammation. T cells in tonsils are fully responsive and competent for antigen-induced cytokine production in RAT and PTA. One should be aware that tonsillectomy, if indicated, might remove a functioning immune organ. Tonsillotomy might be an alternative even in adults to maintain immunological function.