European cytokine network最新文献

Background: Hepatitis C virus (HCV) is the leading cause of chronic liver diseases including hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. We aimed to assess serum levels of interleukin (IL)-22, IL-27 and IL-35 in patients with hepatitis C and healthy controls to investigate their possible relationship with viral genotypes and liver enzyme levels.

Method: A total of 30 newly diagnosed hepatitis C patients with no history of antiviral therapy and 30 healthy individuals participated in this study. Serum levels of IL-22, IL-27 and IL-35 were determined by ELISA in peripheral blood samples from patients prior to and following treament with pan-genotypic direct-acting anti-viral therapy. Serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were measured to determine any possible association between hepatic enzymes and cytokine serum levels concentrations.

Result: The results show elevated serum levels of of IL-35 in HCV-infected patients compared to treated cases and healthy controls, whereas there was no significant difference in IL-22 and IL-27 serum levels among the three groups. Additionally, the cytokine levels were not significantly correlated with certain genotypes and levels of liver enzymes.

Conclusion: Our findings indicate a potential role for IL-35 in chronic HCV infection and therapeutic management of patients with hepatitis C infection.

Type 2 diabetes (T2D) causes profound psychological and physical distress to patients and burdens the health-care system. Although several antidiabetic drugs have been approved, none of them are adequately effective in the long-term management of T2D. Therefore, novel treatment options are needed for disease prevention or delaying disease progression. Bruton's tyrosine kinase (BTK) is a cytoplasmic enzyme that plays a role in B-cell differentiation and proliferation, and therapeutic targeting of BTK offers protection against chronic diseases. In this study, we analyzed BTK expression and its correlation with inflammatory mediators in patients with diabetes and obesity. The levels of BTK were significantly high in visceral adipose tissues of patients (p < 0.01) with diabetes and obesity compared with healthy controls. Additionally, a positive correlation was noted between the expression of BTK and the inflammatory cytokine genes TNF-α, INF-γ, IL-6, and IL-1 (p < 0.01) in adipose tissue. In insulin-resistant HepG2 cells (IR-HepG2), ibrutinib inhibited BTK expression in parallel with inflammatory genes, and increased insulin signaling and activity compared with untreated IR-HepG2 cells. Additionally, ibrutinib-treated IR-HepG2 cells showed increased glucose uptake compared with untreated IR-HepG2 cells. These results provide evidence that BTK inhibition may serve as a novel therapeutic strategy for the treatment of T2D. These findings also uncover the novel role of BTK in diabetes and insulin resistance; however, further in vivo studies are required prior to translating the findings into clinical settings.

Tuberculosis (TB) is one of the leading infectious causes of death worldwide and despite the progress recently made in TB control at a global level, the decline in its incidence is still slow. It is therefore crucial to evaluate the performance of new tools for monitoring of TB treatment. The aim of this study was to evaluate the response to tuberculosis treatment using the QuantiFERON-TB Gold Plus (QFT-Plus) kit. Blood samples of 100 patients with active TB were taken before treatment and after three months, if treatment was successful and sputum culture was negative. Whole blood was incubated in the presence or absence of the TB antigens, TB1 and TB2-specific antigens, and the production of IFN-γ was determined using the QuantiFERON-TB Gold Plus (QFT-Plus) test. The data were analyzed using SPSS 16 software and statistical significance was assessed at a two-tailed P value of 0.05. The median values of IFN-γ released following stimulation with TB1 peptides decreased slightly after treatment (2.5 IU/mL (IQR: 0.9-5.3), compared to the baseline (3.4 IU/mL (IQR: 0.5-6.6)). Also, with respect to the TB1 antigen, 38 out of 45 patients were positive for the QFT test before treatment (84.4%) and 37 cases after treatment (82.2%). On the other hand, the median values of IFN-γ determined with the TB2 test declined marginally after treatment (2.7 IU/mL; IQR: 0.95-5.8), as compared to pretreatment (3.0 IU/mL; IQR: 0.7-8.9). Thirty-nine out of 45 patients (86.7%) before initiation of treatment and 37 cases following a 3-month treatment (82.2%) were had positive values. Moreover, the median values of IFN-γ of TB2 minus TB1 before and after treatment were 0.17 (IQR: 0-1.0) and 0.03 (IQR: 0.0.48), respectively; however, these differences were not significant (p value=0.29). Conclusion: The results of this study show no significant differences between the IFN-γ release in TB patients prior to and after treatment. However, more extensive studies are needed in different populations with higher sample sizes to validate these results.

Coronavirus disease (COVID-19) reached pandemic proportions at the beginning of 2020 and continues to be a worldwide concern. End organ damage and acute respiratory distress syndrome are the leading causes of death in severely or critically ill patients. The elevated cytokine levels in severe patients in comparison with mildly affected patients suggest that cytokine release syndrome (CRS) occurs in the severe form of the disease. In this paper, the significant role of pro-inflammatory cytokines, including IL-1, IL-6, and TNF-alpha, and their mechanism of action in the CRS cascade is explained. Potential therapeutic approaches involving anti-IL-6 and anti-TNF-alpha antibodies to fight COVID-19 and reduce mortality rate in severe cases are also discussed.

Natural cannabinoids may have beneficial effects on various tissues and functions including a positive influence on the immune system and the inflammatory process. The purpose of this study was to investigate the effects of natural cannabinoids on the production of pro-inflammatory cytokines by lipopolysaccharide (LPS)-stimulated whole human blood cells. Levels of the pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured before and after exposure of LPS-stimulated whole blood to different concentrations of Cannabidiol (CBD) or a combination of CBD and Tetrahydrocannabinol (THC) extract. LPS stimulated the production of the pro-inflammatory cytokines. Exposure to both CBD and CBD/THC extracts significantly suppressed cytokine production in a dose-dependent manner. Exposure to cannabinoid concentrations of 50 μg/ml or 100 μg/ml resulted in a near-complete inhibition of cytokine production. This study demonstrates that natural cannabinoids significantly suppress pro-inflammatory cytokine production in LPS-stimulated whole blood in a dose-dependent manner. The use of human whole blood, rather than isolated specific cells or tissues, may closely mimic an in vivo sepsis environment. These findings highlight the role that natural cannabinoids may play in suppressing inflammation and call for additional studies of their use as possible novel therapeutic agents for acute and chronic inflammation.

Introduction and aim: Breast cancer (BC) is one of the top three common cancers in women, responsible for nearly one-third of all new cancer diagnoses. Angiogenesis plays a crucial role in BC progression. In this study, we aimed to measure the serum concentrations of eight angiogenic factors in BC patients and healthy controls and to assess their correlation with clinicopathological variables.

Methods: In a case-control study, 62 pathologically confirmed BC patients as well as 54 age-matched controls were recruited. A bead-based immunoassay was used to measure serum levels of VEGF-A, ANG-2, PDGF-AA, PDGF-BB, EGF, TGF-α, HGF, and bFGF.

Results: We observed a significant elevation in serum levels of VEGF-A, EGF, and PDGF-AA in BC patients compared with the controls (P < 0.05). Patients with grade III had higher ANG-2 levels compared with those with grades I (P = 0.007) and II of the disease (P = 0.003). In addition, estrogen-positive and progesterone-positive BC patients had higher levels of TGF-α (P < 0.05).

Conclusion: The significant elevation of VEGF-A, EGF, and PDGF-AA serum levels in BC patients suggests these cytokines might have diagnostic value as potential biomarkers in BC. Further large-scale studies are needed to generalize these results to all BC patients.

Background: Evidence links COVID-19 severity to hyper-inflammation. Treatment with tocilizumab, a monoclonal antibody directed against the interleukin-6 (IL-6) receptor, was shown to lead to clinical improvement in patients with severe COVID-19. We, therefore, performed the present systematic review and meta-analysis to investigate whether the circulating levels of IL-6 is a reliable indicator of disease severity among patients affected with COVID-19.

Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar on April 19, 2020.

Results: Eleven studies provided data of IL-6 levels in patients with severe to critical COVID-19 (severe) and patients with mild to moderate COVID-19 (non-severe). The included studies were of moderate to high quality. The mean patients' age was 60.9 years, ranging from 45.2 to 76.7 years in the severe group and 46.8 years, ranging from 37.9 to 61 years, in the nonsevere group. Fifty-two percent were male in the severe group, as compared to 46% in the non-severe group. An overall random effects meta-analysis showed significantly higher serum levels of IL-6 in the severe group than in the non-severe group with a mean difference of +23.1 pg/mL (95% CI: 12.42-33.79) and the overall effect of 4.24 (P-value < 0.001). Meta-regressions showed that neither age nor sex significantly influenced the mean difference of IL-6 between the groups.

Conclusions: Meta-analysis and meta-regression reveal a reliable relationship between IL-6 and COVID-19 severity, independent of age and sex. Future research is, however, required to assess the effect of BMI on the pattern of IL-6 production in patients with COVID-19. Also, there might be confounding factors that influence the relationship between IL-6 and COVID-19 severity and remain as yet unknown.

Atherosclerosis is initiated when lipoproteins are trapped by proteoglycans in the arterial intima. Macrophages play a vital role in this disease, especially in the formation of foam cells and the regulation of pro-inflammatory responses. They also participate in plaque stabilization through the secretion of matrix metalloproteinases. Studies have reported the role of ADAMTS proteases in osteoarthritis and atherosclerotic lesions.In the present study, we have studied the effect of interleukin-17A (IL-17A) on the expression of ADAMTS-5 in the macrophage cell line THP-1. The results show that the mRNA and protein expression levels of ADAMTS-5 were significantly upregulated when differentiated THP-1 cells were treated with 100 ng/mL of IL-17A for 24 h with maximum ADAMTS-5 mRNA expression levels obtained at 8 h of stimulation. Subsequent inhibition studies showed that IL-17A upregulation of ADAMTS-5 was mediated through ERK and JNK pathways in THP-1 cells. Phosphorylation studies revealed that the expression of ADAMTS-5 transcripts was upregulated by IL-17A through the activation of p-c-Raf (S338), p-MEK1/2 (Ser217/221), p-p44/42 MAPK (Thr202/Tyr204), and p-Elk1 (Ser383). ERK1/2 siRNA transfection further confirmed that the ERK pathway is involved in the expression of ADAMTS-5 in IL-17A-stimulated THP-1 cells.

Along with the developing technology in the modern age, physical activity had decreased considerably in children and adolescents alike with a concomittant and rapid increase in the prevalence of childhood obsesity. The purpose of the present study is to measure the levels of serum nesfatin-1 and irisin in obese children. The present study was carried out with a total of 62 children, including 32 obese children diagnosed between June 2017 and October 2017 and 30 healthy children. Serum nesfatin-1, irisin, SOD, MDA, fasting blood glucose, total cholesterol (TC), triglyceride (TG), HDL-C, LDL-C, aspartate amino transferase (AST), alanine amino transferase (ALT)), blood urea nitrogen (BUN), C-reactive protein (CRP), calcium (Ca), sodium (Na), potassium (P), chromium (Cr), ferritin, and vitamin B₁₂ data were collected for each patient. In our study, mean nesfatin-1 and SOD values of the obesity group were lower than those of the control group (p <0.05, p <0.001), whereas irisin and MDA values were higher than those of the control group (p <0.001). Childhood obesity is still a significant global problem, despite increased social awareness and numerous preventive healthcare interventions. We believe that all the prospective studies to be carried out to evaluate the relationship between obesity-irisin-nesfatin-1 triad, will make positive contributions to treatment of obesity.

Special hormonal and immunological changes are required for normal pregnancy continuation. To escape from rejection by the maternal immune system, pregnancy needs an optimum environment with the integration and the balance of immune factors. As an immunologically unique site that permits allogenic fetus to be tolerated by mother, the maternal-fetal interface has a vital role. Microorganisms may trigger innate immune responses at the maternal-fetal interface and this may have a significant impact on the success of pregnancy. While the presence of inflammatory markers are slightly increased in healthy pregnancies, their significant increase in preeclampsia suggests that the balance between the inflammatory and antiinflammatory mechanisms may be disrupted by a shift towards inflammation. Based on these immunological observations, we aimed to review the literature for the link between the inflammatory response and preeclampsia since its etiology has not yet been clarified.