Correlation of Serum Levels of Interleukine-16, CCL27, Tumor Necrosis Factor-related Apoptosis-inducing Ligand, and B-cell Activating Factor with Multiple Sclerosis Severity.

The pathogenic roles of Interleukine-16 (IL-16), CCL27, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and B-cell activating factor (BAFF) has been shown in some autoimmune and inflammatory diseases. We aimed to correlate the circulatory changes of such factors with the severity of disease in patients with multiple sclerosis (MS). This case-control study was conducted on 84 MS patients and 83 healthy controls. We measured the serum levels of IL-16, CCL27, TRAIL, and BAFF in all participants by enzyme-linked immune sorbent assay. Using the expanded disability status scale (EDSS), we evaluated the severity of MS. Finally, we assessed the correlation between serum levels of such factors with the severity of MS. We found increased serum levels of CCL27, IL-16, and BAFF in patients with MS compared to those in healthy subjects. However, no difference was found in serum levels of TRAIL between the patients and controls. In addition, a significant positive correlation between serum levels of CCL27, IL-16, TRAIL, and BAFF with disease severity according to EDSS score was determined. We showed higher serum levels of CCL27, BAFF, TRAIL, and IL-16 in MS patients with more severe disabilities than mild forms. Such finding may represent their contribution to the pathogenesis of MS. Blocking such molecules may yield new treatments for MS.

The Relationship between Serum and Gene Expression Levels of RANK, RANKL and Osteoprotegerin Inflammatory Pathway with Unstable Angina: A Case-control Study.

 Osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B (RANK) and receptor activator of nuclear factor-kappa B ligand (RANKL), the members of the tumor necrosis factor (TNF) family, have multiple effects on bone metabolism, endocrine functions and, as an inflammatory pathway, in the immune system. This study tried to determine the association of the OPG/RANKL/RANK axis with the severity of unstable angina (UA) as an inflammatory condition. Our study involved 50 patients with UA and 50 healthy people. Serum and peripheral blood mononuclear cells were isolated from all participants. Serum levels and gene expression of OPG, RANKL, and RANK in mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. For each patient with UA, the thrombolysis in myocardial infarction (TIMI) and the global registry of acute coronary events (GRACE) scores were determined to evaluate the severity of the disease. Then we analyzed the relation of OPG, RANKL, and RANK levels with TIMI and GRACE scores in patients with UA. Discriminate analysis was used to predict the combinational models of such factors on the prediction of UA. Serum levels of OPG and RANKL (p<0.001) and gene expression of RANKL (p<0.001) were significantly more in patients than those in healthy ones. No relation was seen between the OPG/RANKL/RANK axis and the severity of UA according to TIMI and GRACE scores. Our study shows that serum level, as well as gene expression of OPG/RANKL/RANK axis neither, predicts the occurrence of UA nor shows any relationship with its severity.

Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial.

BACKGROUND: Cytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS. METHODS: This study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1g/day) or a matched placebo for a period of 8 weeks. RESULTS: One hundred and seventeen subjects were assigned to either curcumin (n=59) or placebo (n=58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-ß and MCP-1 following curcumin supplementation (p<0.001). In the placebo group, serum levels of TGF-ß were decreased (p=0.003) but those of IL-6 (p=0.735), TNF-α (p=0.138) and MCP-1 (p=0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-ß and MCP-1 in the curcumin versus placebo group (p<0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines. CONCLUSION: Results of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.

Effects of supplementation with curcumin on serum adipokine concentrations: A randomized controlled trial.

OBJECTIVE: Previous experimental studies have suggested curcumin as a safe phytochemical that can improve insulin resistance through effects on adiponectin and leptin. This study aimed to investigate the effect of curcumin on circulating adiponectin and leptin concentrations in patients with metabolic syndrome. METHODS: In this pilot, randomized, double-blind, placebo-controlled trial, subjects who met the criteria of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria were randomly assigned to curcumin (n = 59; 1000 mg/d) or a placebo (n = 58) for 8 wk. Serum adiponectin and leptin concentrations were determined before and after intervention. The pooled effect size for the impact of curcumin supplementation on serum adiponectin and leptin levels was also estimated using random-effects metaanalysis. RESULTS: Eight-week supplementation with curcumin was associated with a significant increase in serum adiponectin levels (P < 0.001) and a reduction in serum leptin concentrations (P < 0.001). Serum leptin:adiponectin ratio was also improved by curcumin (P < 0.001). These beneficial effects of curcumin remained significant after adjustment for changes in serum lipids and glucose concentrations and baseline differences in body mass index and serum levels of glucose and glycated hemoglobin as potential confounders of treatment response. Metaanalysis suggested that curcumin supplementation can increase adiponectin levels by 76.78% (95% CI: 6.14-147.42; P = 0.0330), and reduce leptin by 26.49% (95% CI: -70.44 to 17.46), however this latter effect size did not reach statistical significance (P = 0.238). CONCLUSIONS: Curcumin can improve serum levels of adiponectin and leptin in patients with metabolic syndrome. This trial was registered at the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/) under Trial No. UMIN000018339.

Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis.

BACKGROUND: Oxidative stress and inflammation have been proposed as emerging components of metabolic syndrome (MetS). Curcuminoids are natural polyphenols with strong antioxidant and anti-inflammatory properties. OBJECTIVE: To study the effectiveness of supplementation with a bioavailable curcuminoid preparation on measures of oxidative stress and inflammation in patients with MetS. Our secondary aim was to perform a meta-analysis of data from all randomized controlled trials in order to estimate the effect size of curcuminoids on plasma C-reactive protein (CRP) concentrations. METHODS: In this randomized double-blind placebo-controlled trial, 117 subjects with MetS (according to the NCEP-ATPIII diagnostic criteria) were randomly assigned to curcuminoids (n = 59; drop-outs = 9) or placebo (n = 58; drop-outs = 8) for eight weeks. Curcuminoids were administered at a daily dose of 1 g, and were co-supplemented with piperine (10 mg/day) in order to boost oral bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of malondialdehyde (MDA) and CRP were measured at baseline and at study end. Regarding the importance of CRP as a risk marker and risk factor of cardiovascular disease, a random-effects meta-analysis of clinical trials was performed to estimate the overall impact of curcuminoid therapy on circulating concentrations of CRP. The robustness of estimated effect size was evaluated using leave-one-out sensitivity analysis. RESULTS: Supplementation with curcuminoid-piperine combination significantly improved serum SOD activities (p < 0.001) and reduced MDA (p < 0.001) and CRP (p < 0.001) concentrations compared with placebo. Quantitative data synthesis revealed a significant effect of curcuminoids vs. placebo in reducing circulating CRP concentrations (weighed mean difference: -2.20 mg/L; 95% confidence interval [CI]: -3.96, -0.44; p = 0.01). This effect was robust in sensitivity analysis. CONCLUSIONS: Short-term supplementation with curcuminoid-piperine combination significantly improves oxidative and inflammatory status in patients with MetS. Curcuminoids could be regarded as natural, safe and effective CRP-lowering agents.

Th1/Th2 cytokines in patients with Graves' disease with or without ophthalmopathy.

About 25-50% of Graves' disease (GD) patients develop thyroid eye diseases, which is associated with inflammatory process and abnormalities in the levels of several cytokines in orbital tissues in GD. The aim of this study was to determine the Th1 and Th2 serum cytokines in patients with GD with or without ophthalmopathy. Serum levels of cytokines and autoantibodies including Interferon-gamma (IFN-γ), Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-10 (IL-10), TSH receptor autoantibody (TRAb), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody(TgAb) were measured by enzyme linked immunosorbent assay(ELISA) in 34 patients with GD and in 33 normal controls. Patients were also divided in two subgroups: 18 cases with ophthalmopathy and 16 cases without ophthalmopathy. Cytokine and antibody responses were analyzed in both groups. Compared with control subjects, patients with GD showed elevated levels of IL-2 and IL-10. IFN-γ levels were lower in patients in comparison to the controls. No significant differences were found between patients and controls regarding the IL-4. There was no statistically significant difference in cytokine levels between those with or without ophthalmopathy. Quantitative-cytokine analysis demonstrated that a combination of Th1 and Th2 cytokines may contribute to the pathogenesis of GD. These results also indicate that IL-10, but not IL-4, is related to the moderate and severe forms of thyroid associated ophthalmophathy.