Cytokine Levels In Patients Research Articles

Proportion of natural killer cells in peripheral blood lymphocytes is correlated with cytokine levels in patients with type 2 diabetes mellitus and prediabetes: a preliminary report

Proportion of natural killer cells in peripheral blood lymphocytes is correlated with cytokine levels in patients with type 2 diabetes mellitus and prediabetes: a preliminary report

Active vitiligo vulgaris following the administration of the Oxford–AstraZeneca (AZD1222) vaccine against SARS-CoV-2

Sir, There is significant uncertainty surrounding vaccines against COVID-19. Due to the critical need, these vaccines are being developed and approved at a uniquely fast pace [1]. Currently, the approved vaccines take their action by administering the host with sequences encoding the viral spike protein. This essentially means that these gene-therapy-based vaccines, whose long-term effects remain unknown, are going to be administered globally [2]. Therefore, despite their safety and efficacy demonstrated in respective clinical trials, it is reasonable to be cautious and adopt more intensive post-marketing vigilance [3]. A forty-nine-year-old diabetic male presented with asymptomatic, rapidly growing, leukodermal patches on the scalp (Fig. 1), which began to appear suddenly fourteen days following the administration of the first dose of the Oxford–AstraZeneca (AZD1222) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The patches were clinically consistent with vitiligo and were confirmed with their well-defined, ivory-white patches by Wood’s lamp examination (Fig. 2).There were no leucodermic patches anywhere else on the body, no family history of vitiligo, and no history of COVID-19 viral infection. After one week of reevaluation, the patch increased in size. The patient also presented with cellulitis on the right groin persistent for three days and was treated with an antibiotic with a follow-up. All baseline investigations, including a full blood count and renal and liver function tests, were normal. The patient is currently on follow-up. Cytokines play a role in regulating the immune response and the depigmentation process in vitiligo. There is an imbalance in cytokine levels in patients with vitiligo. IFN-g expression plays a role in the autoimmune process in vitiligo. The expression of the cytokine IFN-g is associated with melanocyte destruction in the active phase of vitiligo lesions [4]. IFN-g interacts with the viral receptor, resulting in the consequent reduction of several virus replicating, down-regulating genes and gene products [5]. Li et al. [6] demonstrated that IFNs are potential drug choices for SARS-CoV-2 infection. Here, we hypothesize that patients with non-segmental vitiligo (NSV), an autoimmune skin (and mucosal) disorder, may clear SARS-CoV-2 infection more efficiently and have a lower risk of COVID-19 development. Conversely, in the case of COVID-19 development, vitiligo autoimmunity may influence the cytokine storm-related disease burden. In addition, immune activation during SARS-CoV-2 infection or COVID-19 disease may increase vitiligo disease activity. Our hypothesis is based on the shift of the immune system in NSV toward adaptive type 1 (IFNg and CD8 T cells) and innate immune responses [7]. It is unclear whether the vitiligo in our patient was caused by vaccination, However, the temporal relationship between the vaccine and the development of the disease is interesting. We may, therefore, conclude that our patient had his latent vitiligo activated by the vaccine. Yet, further work is needed to demonstrate a causal relationship between vitiligo and COVID-19 vaccination. To the best of our knowledge, this is the first reported case of vitiligo associated with the administration of the Oxford–AstraZeneca (AZD1222) vaccine.

OPTIONS OF CORRECTING INSULIN RESISTANCE AND PROINFLAMMATORY CYTOKINE LEVELS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

The objective of this study was to investigate the effect of empagliflozin on insulin resistance, leptin and proinflammatory cytokine levels in patients with type 2 diabetes. Materials and methods. 100 patients with type 2 diabetes with normal weight, overweight and obesity of various degrees were examined. Anthropometric indicators were taken. Levels of leptin, IL-6, CRP in blood serum were determined, HOMA index was calculated. Results. Insulin resistance in all groups of patients was associated with abdominal obesity, hyperleptinemia (r = 0.505, p < 0.05), (r = 0.846, p < 0.05), (r = 0.886, p < 0.05), (r = 0.736, p < 0.05) in patients from Group I-IV. Patients of all examined groups have shown a significant increase in IL-6 levels, compared with the control group (p < 0.05), but the level of IL-6 in patients from Group II, III and IV have been significantly higher than those from Group I (p < 0.05) and the control group (p < 0.05) and has increased along with the weight gain. Similarly, the highest indices of CRP levels have been found in patients from Group IV which proves a high pro-inflammatory activity in these patients with type 2 diabetes and obesity. After a 6-month course of treatment patients taking empagliflozin, regardless of BMI, have shown significantly decreased levels of both IL-6 (p < 0.05), and CRP (p < 0.05). Levels of leptin (p < 0.05) and HOMA index (p < 0.05) were significantly reduced in obese patients, too. Conclusions. As a result of the study, it has been established that the use of empagliflozin in the dose of 10 mg per day for 6 months has had a significant effect on anthropometric parameters and markers of insulin resistance (HOMA index, leptin) in patients with type 2 diabetes and obesity. A significant decrease in the levels of IL-6 and CRP under the influence of empagliflozin, regardless of the patient’s weight has been revealed.

Gut microbiota and plasma cytokine levels in patients with attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood mental disorder with undetermined pathophysiological mechanisms. The gut microbiota and immunological dysfunction may influence brain functions and social behaviours. In the current study, we aimed to explore the correlation of gut microbiome imbalance and inflammation in the pathophysiology of ADHD. Forty-one children with ADHD and thirty-nine healthy-control (HC) individuals were recruited. Faecal samples from all participants were collected and submitted for 16 S rRNA V3–V4 amplicon microbiome sequencing analysis. The plasma levels of 10 cytokines, including TNF-α, IL-6, IL-1β, IL-2, IL-10, IL-13, IL-17A, IFN-α2, IFN-γ, and MCP-1, were determined using a custom-made sandwich enzyme-linked immunosorbent assay (ELISA) developed by Luminex Flowmetrix. There was no significant difference between the ADHD and HC groups in species diversity in the faeces, as determined with α-diversity and β-diversity analysis. In the ADHD group, three differentially abundant taxonomic clades at the genus level were observed, namely Agathobacter, Anaerostipes, and Lachnospiraceae. Top differentially abundant bacteria and representative biological pathways were identified in children with ADHD using linear discriminant analysis (LDA) effect size (LEfSe), and the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis, respectively. The plasma levels of TNF-α were significantly lower in children with ADHD than in HCs. Within the ADHD group, the levels of TNF-α were negatively correlated with ADHD symptoms and diversity of the gut microbiome. Our study provides new insights into the association between gut microbiome dysbiosis and immune dysregulation, which may contribute to the pathophysiology of ADHD.

Mindfulness-based stress reduction may decrease stress, disease activity, and inflammatory cytokine levels in patients with autoimmune hepatitis

Background & AimsPsychological and life stressors may impact autoimmune hepatitis (AIH) disease activity and increase relapse risk. Mindfulness-based stress reduction (MBSR) is a validated course that reduces stress reactivity, and improves stress and emotion regulation. This single-arm exploratory pilot study of adult patients with AIH aimed to define the impact of an 8-week MBSR program on quality of life, disease activity, and cytokine mediators.MethodsThe perceived stress survey-10 (PSS) and the brief self-control scale (BSCS) measured subjective distress and self-control. Serum alanine aminotransferase (ALT) and cytokine levels were measured, and immunosuppressant doses recorded.ResultsSeventeen patients completed the MBSR program. Post-MBSR, 71% (n = 12) showed PSS score improvement at 8 weeks vs. baseline (median 15 vs. 21, p = 0.02). At 12 months, PSS improvement persisted vs. baseline (median 15 vs. 21, p = 0.02). Post-MBSR, 71% (n = 12) showed BSCS score improvement at 8 weeks vs. baseline (median 4.1 vs. 3.8, p = 0.03). At 12 months, the median BSCS score remained significant (3.9 vs. 3.8, p = 0.03). After the 8-week MBSR, the 35% of patients with ALT >34 U/L had a median ALT reduction (44.5 vs. 71.5 U/L, p = 0.06), whereas the 71% of patients on prednisone had significant dose reductions (5.75 vs. 10 mg, p = 0.02) which persisted at 12 months vs. baseline (3.75 vs. 10 mg, p = 0.02) without a compensatory increase in steroid-sparing dosing. Significant improvement was noted in peripheral blood cytokine levels (IL-6, IL-8, IL-10, IL-17, IL-23, and sCD74/MIF ratio) from baseline to 8 weeks.ConclusionsMBSR significantly improved perceived stress and self-control scores while decreasing ALT levels, steroid requirements, and inflammatory cytokine levels in this pilot study in adult AIH. Stress modification may impact quality of life and disease activity, and should be further evaluated as an intervention in AIH.Clinical Trials registrationThis study is registered at ClinicalTrials.gov (NCT02950077).Lay summaryAutoimmune hepatitis can reduce quality of life and mental health, while stress may impact autoimmune hepatitis itself. We piloted mindfulness-based stress reduction as a strategy to reduce stress in adult patients with autoimmune hepatitis and found that the intervention reduced perceived stress and may have also impacted the disease by improving inflammation and medication needs. Stress reduction should be further studied to improve quality of life and possibly to impact disease activity in autoimmune hepatitis.

The effect of aripiprazole on leptin levels of patients with chronic schizophrenia and a comparison of leptin, acute phase protein, and cytokine levels with regard to body mass and body composition indexes.

The aim of this study was to test the effect of aripiprazole on leptin, insulin, acute phase proteins, and selected cytokines levels in patients with chronic schizophrenia. Additionally, levels of leptin, insulin, acute phase proteins, and cytokines were compared with body mass and body composition indexes. Levels of leptin, insulin, serum amyloid A (SAA), tumour necrosis factor alpha (TNF-α), and interleukins 17A (IL-17A) and 18 (IL-18) in blood serum were measured for 17 patients before and after 28 days of administering aripiprazole by means of enzyme-linked immunosorbent assay (ELISA). Before and after the study, body mass and waist circumference (WC) were also measured, and body mass index (BMI) and body fat percentage (BF%) were estimated. The sex of each patient was taken into account. After administration of aripiprazole the reduction of levels of leptin, insulin, SAA, and TNF-a were statistically significant, similarly to body mass reduction and decrease in WC, BMI, and BF%, which were also statistically significant. A positive correlation between leptin and BF% and negative correlation between insulin and body mass and body composition indexes were observed before and after the study. High sensitivity C-reactive protein (hsCRP) and hsCRP/albumin positively correlated with BMI before the treatment. In the group of women a statistically significant positive correlation between TNF-α and IL-17A and body mass and body composition indexes was observed, and in the group of men a negative correlation between IL-18 and BMI, WC, and BF% was noted. The effect of aripiprazole is connected to its anti-inflammatory activity. A 28-day treatment resulted in reduction of adipose tissue, and in the group of women it returned their leptin sensitivity to normal levels. A change of psychotropic treatment and administration of aripiprazole reduces cardiometabolic risks.

Inflammatory Cytokine Levels in Patients with Sporadic Amyotrophic Lateral Sclerosis

Objectives: In the present study, inflammatory factors, including interleukin (IL) and tumor necrosis factor-α (TNF-α) in the peripheral blood of patients with sporadic amyotrophic lateral sclerosis (sALS), were evaluated, and the issue of whether these variables were associated with the progression and severity of the disease examined. Methods: Data on inflammatory factors, including IL-1, IL-2, IL-6, IL-8, IL-10, and TNF-α, were retrospectively collected from 248 sALS patients admitted to the Chinese PLA General Hospital between March 2018 and March 2021. The relationships between the variables and clinical features, including gender, age at onset, site of onset, time from onset to hospital admission, ALS functional rating scale score, and diagnostic category were analyzed. Results: IL-1, IL-2, IL-6, IL-8, IL-10, and TNF-α levels were elevated in 43.75%, 7.04%, 16.42%, 25.35%, 1.41%, and 50.72% of ALS patients, respectively, compared with the normal value range. IL-2 and IL-6 levels were inversely associated with the ALS functional rating scale score (r = −0.280, p = 0.004 and r = −0.198, p = 0.048). Conclusion: Elevated levels of inflammatory cytokines support the hypothesis of an inflammatory response in ALS, and IL-2 and IL-6 may be used as an inflammation-related biomarker for disease severity.

Immune Modulation and Cytomegalovirus Reactivation in Sepsis-induced Immunosuppression: A Pilot Study.

IntroductionSepsis is a life-threatening condition caused due to dysregulated immune response to an infection and progressive immunosuppression. Reactivation of cytomegalovirus (CMV) occurs frequently in sepsis and is found associated with adverse outcomes. The study objective was to evaluate the association between incidence of CMV reactivation and immune alteration in sepsis-induced immunosuppression in patients with prolonged sepsis.Patients and methodsPatients admitted to intensive care unit (ICU), with severe sepsis and CMV immunoglobulin G (IgG) seropositivity, were prospectively enrolled. Other manifest immune suppression causes were excluded. Samples were collected on enrolment and further once a week until day 21 or death/discharge. CMV viral load was quantified using qPCR. Lymphocyte subset analysis (CD3+, CD4+, CD8+, CD19+, CD16+/CD56+, and CD25+CD127− regulatory T cells), human leukocyte antigen-DR isotype (HLA-DR) expression on monocytes, programmed death-1 (PD-1) expression on T lymphocytes, and proinflammatory (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ)), anti-inflammatory cytokines levels (IL-2, IL-4, and IL-10) were analyzed by flow cytometry as markers for immunosuppression.ResultsA total of 25 CMV IgG-positive patients and 11 healthy controls were included. CMV reactivation occurred in 20 patients. Patients with CMV reactivation had T-cell lymphopenia. PD-1 expression on CD4+ and CD8+ T cells was markedly elevated (p <0.02) in CMV-reactivated patients compared to nonreactivated patients. HLA-DR expression was significantly low on monocytes in all septic patients (p <0.01) compared to healthy controls. IL-6 levels showed elevation at day 7, whereas IL-10 was found to be significantly higher from day 0 in CMV-reactivated group.ConclusionOur study concluded that immune suppression markers and cytokine levels in patients with severe sepsis were found to be significantly associated with the incidence of CMV reactivation.How to cite this articleLambe G, Mansukhani D, Khodaiji S, Shetty A, Rodrigues C, Kapadia F. Immune Modulation and Cytomegalovirus Reactivation in Sepsis-induced Immunosuppression: A Pilot Study. Indian J Crit Care Med 2022;26(1):53–61.

Cytokine Levels in Patients with β-Thalassemia Major and Healthy Individuals: a Systematic Review and Meta-Analysis.

Cytokine levels in patients with β-thalassemia major (β-TM) have been assessed in several studies. Accordingly, a wide variety of immune disturbances has been shown in patients with thalassemia. Recurrent transfusions cause iron overload, which induces an increase in the production of cytokines. However, no systematic approach or meta-analysis has been done to provide a clear feature of cytokine levels in β-TM. The present meta-analysis aimed to summarize the existing evidence regarding different levels of cytokines in patients with Β-TM compared to healthy controls. This study was performed according to the PRISMA checklist. A systematic search was done in Web of Science (ISI), Scopus, and PubMed databases. The quality of the included studies was assessed based on the New-castle-Ottawa Scale. Meta-analysis was run via STATA 13 software. The standardized mean difference was considered the effect size for comparing the continuous variables. This meta-analysis included 16 studies conducted on 805 β-TM patients and 624 healthy individuals (with the mean age of 16.10 ± 4.33 and 16.22 ± 3.78, respectively). The results showed significantly higher levels of Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and IL-10 in patients with β-TM compared to the healthy controls. The results indicated that the levels of both inflammatory and anti-inflammatory cytokines were higher in patients with β-TM compared to the healthy population, which could be associated with higher levels of oxidative markers in these patients. Further studies are suggested to evaluate the difference in cytokine levels among different types of thalassemia.

Changes of th1 and th2 cytokines levels among sudanese tuberculosis patients during treatment.

The interaction of T cells with infected macrophages depends on the interplay of cytokines produced in each cell, and this mechanism is a key to protective immunity against Mycobacterium tuberculosis. Extensive research has been devoted to studying the changes in systemic cytokine levels in patients with tuberculosis (TB), but the results are inconclusive. Determine Th1 and Th2 cytokine immune response levels among new TB patients compared to follow-up and healthy control. Cross-sectional laboratory-based study. Immunology Laboratory, National Center for Research. Blood samples (n = 145) were collected from confirmed new TB cases, follow-up TB cases, and from healthy controls. Participants were initially diagnosed by microcopy using Ziehl-Neelsen smear method and confirmed by polymerase chain reaction using IS6110. Cytokine levels (interleukin-10 [IL-10], tumor necrosis factor alpha [TNF-α], and Interferon-gamma [IFN-γ]) were measured directly from plasma using sandwich enzyme-linked immunosorbent assay. Measuring Th1 cytokines (IFN-γ and TNF-α) and Th2 cytokine (IL-10). One hundred and forty-five cases (new TB cases, 85; follow-up, 25; and healthy control, 35) were included in this study. The study population were mainly males (70.3%) compared to females (29.7%) and 87.5% aged between 21 to 60 year. The plasma IFN-γ levels were found significantly higher in new TB cases (mean 35.38 pg/m; confidence interval: 29.32-41.43) than in the follow-up patients and the healthy control (P = 0.000). There were no significant differences in TNF-α and IL-10 levels among the new TB cases and the follow-up and healthy control (P = 0.852 and P = 0.340, respectively). Direct plasma IFN-γ level can be used in TB patient follow-up as a recovery marker as it correlated well with the appearance of the disease and treatment response.

Role of pathogenic T-helper cells-17 in chronic antibody-mediated rejection in renal allograft recipients

Background: Both T-cell and B-cell activities are interlinked. The role of a new subset of T-helper cells (Th17), which is thought to be more pathogenic than other effector T cells, is not much studied in cases of chronic antibody-mediated rejection (CABMR). Therefore, we aimed to determine the circulating frequency of Th17, Pgp+ Th17, Pgp+ CD4T cell, and serum interleukin (IL)-17A cytokine level in patients of CABMR and stable graft function (SGF). Materials and Methods: We had recruited 42 patients of biopsy-proven CABMR (n = 32) and SGF (n = 10). The frequency of Pgp+ CD4Tcells, Pgp+ Th17 and Th17 cell was quantified in circulating blood by flow cytometry, and IL-17A level was determined in serum by ELISA techniques. Results: We observed that the frequency of Th17 cell (2.30 ± 1.15 and 4.46 ± 2.05; P = 0.003), Pgp+ CD4T (15.73 ± 4.38 and 25.27 ± 5.15; P < 0.001), and Pgp+ Th17 (0.78 ± 0.65 and 2.19 ± 0.93; P < 0.001) was higher in CABMR as compared to that of SGF. The ratio of Th17/CD4T cell (0.077 ± 0.045 and 0.14 ± 0.06; P = 0.004), and Pgp+ CD4T/CD4T cell (0.51 ± 0.14 and 0.81 ± 0.17, P < 0.001) was also higher in CABMR as compared to SGF. Serum cytokine IL-17A level was (42.39 ± 13.25 and 66.97 ± 18.27; P < 0.001) pg/ml was also higher in CABMR than that of SGF. The frequency of Pgp+ Th17 cell was positively correlating with 24-h proteinuria (r = 0.309; P = 0.04), serum creatinine (r = 0.423; P = 0.005), and negatively correlating with eGFR (r = −0.468; P = 0.002). Similarly, the frequency of Pgp+ CD4T cell was positively correlating with 24-h proteinuria (r = 0.351; P = 0.023), serum creatinine (r = 0.310; P = 0.04), and negatively correlating with eGFR (r = −0.414; P = 0.006). Conclusions: Higher Pgp+ TH17 cell is associated with CABMR, proteinuria, and graft dysfuntion.

Profiling and multivariate analysis of serum cytokines in patients with generalized pustular psoriasis

Introduction: Generalized pustular psoriasis (GPP) is a chronic autoinflammatory disease characterized by fever, erythema, and sterile pustules occurring over large areas of the skin. The immunopathogenesis of GPP remains poorly understood. We aimed to profile serum cytokine levels in patients with GPP and analyze treatment-associated changes in cytokine levels. Methods: Twenty-four patients who were diagnosed with GPP and received drug treatment, together with 28 unaffected controls, were recruited in this study. Levels of 27 cytokines in serum samples from pre- and post-treated patients as well as unaffected controls were assessed using a Bio-Plex multiplex immunoassay. Multivariate analysis of cytokine levels and clinical parameters was conducted. Results: Serum levels of interleukins interleukin (IL)-1β, IL-1Ra, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), IFN-γ-induced protein 10 (IP-10), monocyte chemoattractant protein-1, tumor necrosis factor-α, and vascular endothelial growth factor were significantly elevated (p &lt; .05) in patients with GPP compared with controls. Serum levels of IL-6, G-CSF, IL-8, IFN-γ, IL1-Ra, IL-10, IL-13, and IL-1β were correlated with GPP severity (r &gt; 0.4, p &lt; .001). Following treatment, serum levels of IL-6, IL-7, IL-12, IFN-γ, IL-1β, IL-4, IL-8, IL-10, IL-13, G-CSF, and IP-10 were significantly decreased (p &lt; .05) compared with pretreatment levels. Among these cytokines, levels of IL-6, IL-7, IL-8, IL-12, IL-13, and IP-10 were reduced to normal levels. Conclusion: GPP patients exhibited markedly elevated levels of cytokines and chemokines involved in both type 1 and type 2 immune responses, suggesting hypercytokinemia occurs in GPP patients. IL-6 showed the strongest correlation with GPP disease severity and other clinical parameters such as CRP level and fever, thus representing an index for GPP severity. Our data comprehensively documented the cytokine profiles of GPP patients and may provide insights into GPP pathogenesis.

Serological levels of cytokines in irritable bowel syndrome (IBS) patients and non-IBS subjects with and without Blastocystis spp. infection.

The objectives of the present study were to investigate the prevalence of Blastocystis spp. and to determine the levels of some pro-and anti-inflammatory cytokines in patients with irritable bowel syndrome (IBS) and without Blastocystis infection in comparison with non-IBS control individuals. Stool samples were collected from 250 IBS patients and 100 samples from controls, examined for the presence of Blastocystis and the percentage of infection was recorded. After that each group subdivided into two groups: non-IBS subjects not infected with Blastocystis (group 1), non-IBS subjects infected with Blastocystis (group 2), IBS patients not infected with Blastocystis (group 3), and IBS patients infected with Blastocystis (group 4). After that, blood samples were collected from 10 participant from each group and sera were separated and used for measuring the levels of the selected pro- and anti-inflammatory cytokines using ELISA method. The results revealed that about 60% of IBS patients were found infected with Blastocystis while 22% of the subjects in the control group were found infected with this parasite and the difference between the two groups was highly significant (P=0.0001). In addition, the results revealed that IBS patients with Blastocystis showed significantly higher In addition, the results revealed that IBS patients with Blastocystis showed significantly higher serum IL-6 (P=0.0004), IL-10 (P=<0.0001), IL-18 (P=0.0001), IFN-γ (P=<0.0001), and TNF-α (P=<0.0001) when compared with the subjects in the control group. Similarly, the non-IBS subjects infected with Blastocystis showed significantly higher serum IL-6 (P=0.0032), IL-10 (P=0.0001), IL-18 (P=0.0002), IFN-γ (P=0.0001), and TNF-α (P=0.0001) in comparison with the subjects in the control group. In conclusion, the infection with Blastocystis has a significant impact on the levels of all the selected cytokines.

N-Acetylcysteine (NAC) Inhibits Synthesis of IL-18 in Macrophage by Suppressing NLRP3 Expression to Reduce the Production of IFN-γ from NK Cells.

Background N-Acetylcysteine (NAC) had exerted antioxidation and anti-inflammation effects on chronic obstructive pulmonary disease (COPD) patients. However, its effect in regulating interleukin- (IL-) 18 was not fully understood. This study was designed to evaluate the specific mechanism of NAC regulating IL-18. Materials and Methods A total of 112 COPD patients and 103 health individuals were recruited in the study. Cytokine level in patients' serum was measured by enzyme-linked immunosorbent assay (ELISA). A COPD mouse model was established by administration of lipopolysaccharide (LPS) and cigarette smoke. The expression of cytokines was measured by ELISA and flow cytometry. Inflammasome-related protein was measured by Western blot. Result NAC could effectively improve the immune status of COPD patients as well as the COPD mouse model by downregulating proinflammation and inflammation cytokines including IL-1β, interferon- (IFN-) γ, tumor necrosis factor- (TNF-) α, and IL-18. It also had the capability to suppress synthesis of IL-18 in macrophage to inhibit the secretion of IFN-γ from natural killer (NK) cells through influencing the inflammasome-related protein in macrophages. Conclusion NAC could effectively inhibit the production of IL-18 by suppressing NLRP3 expression in macrophages to reduce the production of IFN-γ in NK cells.

Serum cytokines levels in patients with myocardial infarction with non-obstructive and obstructive coronary arteries

Aim. To compare the concentrations of proinflammatory and anti-inflammatory cytokines in patients with myocardial infarction with non-obstructive (MINOCA) and obstructive coronary arteries (MIOCA) in the early postinfarction period and after 1-year follow-up.Material and methods. The study included 40 patients with myocardial infarction (experimental group, 19 patients; control group, 21 patients). Three (15,7%) patients with diagnosed acute myocarditis were excluded from the final analysis. Blood samples were taken upon admission, on the 2nd, 4th and 7th days from hospitalization, and also after 1-year follow-up. Twenty-three parameters were analyzed using multiplex analysis and the Multiplex Instrument FLEXMAP 3D system (Luminex Corporation), as well as the MILLIPLEX map Human Cytokine/ Chemokine Panel II.Results. According to multiplex analysis of blood serum of the studied groups, a comparable increase in proinflammatory cytokines CCL-15, CCL-26, CCL-27 in the early postinfarction period and after 1-year follow-up, as well as antiinflammatory and regenerative cytokines CXCL-12, TPO in the early postinfarction period and after 1-year follow-up. In patients with MINOCA, higher concentrations of the following proinflammatory cytokines were determined: IL-16 upon admission (p=0,03), IL-20 on days 2 and 4 of the early postinfarction period (p=0,005 and p = 0.03), as well as CCL-15 on days 4 and 7 (p=0,05 and p=0,02). After 1-year follow-up, among the proinflammatory cytokines, a greater increase in CCL-21 (p=0,02) was noted in the patients of experimental group. Also, in patients with MINOCA, a greater increase in TPO was determined upon admission and on the 2nd day (p=0,02 and p=0,02), SCF — on the 7th day and after 1-year follow-up (p=0,04 and p=0,04), and LIF on the 4th day of early postinfarction period (p=0,007). In contrast, MIOCA patients showed a greater increase in CXCL-12 levels upon admission (p=0,04). At the same time, patients with MINOCA showed a higher level of C-reactive protein on the 1st day, as well as a higher relative monocyte count after 1-year follow-up.Conclusion. Despite a comparable increase in the cytokines CCL-8, CCL-13, CCL26, CCL-27 in patients of both groups, in patients with MINOCA there was a greater increase in proinflammatory cytokines IL-16, IL-20, CCL-15, CCL-21, and also CXCL-12, LIF, TPO, SCF, which have anti-inflammatory and regenerative activity. After 1 year follow-up, MINOCA patients showed a significant increase in CCL-21 and SCF, with a comparable increase in other proinflammatory cytokines in patients of both groups. A greater increase in proinflammatory cytokines in patients with MINOCA may indicate a more aggressive atherosclerosis course and lead to plaque destabilization followed by ischemic event.

Medical nutrition therapy versus standard nutrition advice in patients with esophageal cancer: effect on inflammatory cytokines and nutritional status

Rationale: Malnutrition is common in patients with esophageal cancer. The purpose of this study was to compare medical nutrition therapy (MNT) with standard Nutritional Advice (NA) in regards to nutritional status and serum cytokine levels in patients during chemoradiation therapy (CRT).

Alterations in Peripheral C-Reactive Protein and Inflammatory Cytokine Levels in Patients with Panic Disorder: A Systematic Review and Meta-Analysis.

BackgroundAccumulating evidence has shown the important role of the inflammatory process in the pathophysiology of mental disorders. However, the relative levels of inflammatory markers in patients with panic disorder (PD) have rarely been evaluated. The aim of the present study was to conduct a systematic review to determine the correlation of peripheral C-reactive protein (CRP) and inflammatory cytokine profiles with PD.MethodsThis study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for quantitative research studies published up to July 31, 2021 that measured peripheral levels of CRP and inflammatory cytokines in people with PD compared with controls. Meta-analysis using a random-effects model was performed for the levels of CRP and inflammatory cytokines with data from three or more studies.ResultsFourteen identified studies met the inclusion criteria. In total, 18 cytokines were evaluated. Markers that were reported in more than 3 studies were included in this meta-analysis. The results showed that peripheral levels of CRP, IL-6, IL-2 and TNF-α were significantly higher in PD patients than in healthy controls, while there was no significant difference in peripheral levels of IL-1β, IL-10 and IFN-γ between groups. Notably, the relevant studies involving IL-6, IL-1β, IL-10 and IFN-γ in PD patients were highly heterogeneous. Similar to meta-analyses of other inflammatory factors in mental disorders, our meta-analysis also reflected differences in participant medication use, comorbid anxiety or depression, sampling methods and detection methods. Eight inflammatory cytokines were reported in only one study, and their expression levels were higher, lower, or unchanged compared with those in healthy controls.ConclusionThere is preliminary evidence to suggest a significant inflammatory response in PD patients, but the role of inflammatory markers in PD remains unclear. Studying inflammatory markers in PD will help to clarify the etiology and pathophysiological mechanisms of the disorder.

Age and sex-specific differences in interleukin 4, interferon gamma, macrophage migration inhibitory factor, and vascular endothelial growth factor levels in the tears of healthy subjects.

To investigate the physiological profile of pro-inflammatory and anti-inflammatory cytokines in tears produced by epithelial cells under the effect of endogenous and exogenous biological factors. Knowing the physiological cytokine profile in tears with its biological characteristics including sex- and age-specific effects is fundamental when tears are analyzed for diagnostic or prognostic purposes in eye diseases. Tear samples were collected from right eye of 45 healthy volunteers (24 males, 21 females) by 5 μl microcapillary tube. Cytokines interleukin 1β, interleukin 10, interleukin 4, interferon gamma, macrophage migration inhibitory factor, and vascular endothelial growth factor were quantified by multiplex Bio-Plex system. The production of macrophage migration inhibitory factor cytokine by epithelial cells on the ocular surface is higher in males compared to females (p = 0.05); actually, most of female tear samples present with undetectable macrophage migration inhibitory factor levels. Our results show the negative correlations between the age and concentrations of interleukin 4 (p < 0.01) and interferon gamma (p < 0.01) in tears, respectively, and positive associations of vascular endothelial growth factor levels with the age above 45 years (p < 0.05). Data in this study indicate that age and sex may affect the physiological levels of cytokines in tears. Consequently, the impacts of biological factors need to be recognized and taken into consideration before the levels of cytokines in patients' tears are analyzed for medical reasons. Concentrations of interleukin 1β and interleukin 10 cytokines, however, are very low in healthy tears and do not seem to be influenced by studied biological factors; therefore, they meet the requirements for analytes suitable for medical diagnostic and prognostic purposes.

Associations between expression of indoleamine 2, 3-dioxygenase enzyme and inflammatory cytokines in patients with first-episode drug-naive Schizophrenia

The indoleamine 2,3-dioxygenase (IDO) enzyme is the first rate-limiting enzyme of the tryptophan degradation pathway in which dysfunction of neuroactive metabolites has been implicated in the pathophysiology of schizophrenia. Inflammatory molecules such as pro-inflammatory cytokines could enhance the activity of IDO. There are few studies on the expression of IDO levels and its correlation with levels of inflammatory cytokines in first-episode drug-naive patients with schizophrenia. One hundred inpatients (female = 33, male = 67) with first-episode drug-naive schizophrenia entered a 6-week, double-blind, randomized, placebo-controlled clinical trial. All individuals were assigned celecoxib or placebo combined with risperidone. Serum levels of IDO and six inflammatory cytokines (IL-1β, IL-6, TNF-α IL-17, IL-4, and INF-γ) were measured. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychotic symptoms. Compared to healthy subjects, patients had significantly elevated levels of IDO and six cytokines at baseline. Over the 6-week treatment period, the decrease in the levels of IDO and TNF-α and the improvement in the PANSS total score, positive scores, and negative scores in the celecoxib group were significantly greater than in the placebo group. There was a significantly positive correlation between IDO levels and the PANSS negative scores and between IDO levels and TNF-α and IFN-γ levels in the celecoxib group. These findings showed abnormal expression of IDO levels which correlated with negative symptoms and pro-inflammatory cytokine levels in patients with first-episode drug-naive schizophrenia, suggesting the important role of IDO in the pathological mechanism of schizophrenia. Registration number: ChiCTR2000041403.

Proinflammatory cytokines levels in patients with temporomandibular joint disorder undergoing arthroscopy.

Biomarkers represent objective indicators of normal processes, pathology, or responses to therapeutic intervention. The purpose of this study is to evaluate the levels of proinflammatory cytokines in synovial fluid of the temporomandibular joint (TMJ) and to investigate whether there is a correlation between elevated levels and disease progression. This is a prospective study that included patients who were diagnosed with internal derangement according to magnetic resonance imaging and were classified according to Wilkes's classifications. After failing to improve with conservative treatment, they were referred for TMJ arthroscopy. During arthroscopy, synovial fluid was collected for biomarker analyses that included the investigation of levels of proinflammatory cytokines: tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and vascular endothelial growth factor (VEGF). The Mann-Whitney U test was used for differences between subgroups for TNF-α, IL-6, and VEGF. During the study period, 22 patients presented with a TMJ disorder and met the criteria of the study. There was a statistically significant correlation between the levels of VEGF, TNF-a, and osteoarthritis (P < 0.05). There was also a statistically significant correlation between TNF-a levels and a higher degree of chondromalacia (P = 0.019). An increase in inflammatory cytokines coupled with chondromalacia propose a more aggressive degenerative disease.