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1.
The efficacy of soy isoflavones combined with soy protein on serum concentration of interleukin-6 and tumour necrosis factor-α among post-menopausal women? A systematic review and meta-analysis of randomized controlled trials.
Gholami, A, Mollanoroozy, E, Reza Baradaran, H, Hariri, M
Clinical and experimental pharmacology & physiology. 2022;(1):10-24
Abstract
The post-menopausal stage in women's life is associated with the enhancement of inflammation that may be reduced using soy isoflavones or soy protein. The present study aimed to summarize the effect of soy isoflavones plus soy protein on circulating interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in post-menopausal women. The English-language articles were identified from the databases such as Cochrane Library, clinicaltrials.gov, Web of Science, PubMed, and Scopus until December 2020. The mean change from baseline and its standard deviation (SD) for intervention and comparison groups were used to calculate the effect size. The statistical heterogeneity of the intervention effects was computing by Cochran's Q test and I2 statistic. Nine and seven studies were selected for systematic review and meta-analysis, respectively. The results of our meta-analysis indicated a non-significant effect on the serum concentrations of IL-6 and TNF-α (weighted mean differences [WMD] = 0.07 pg/mL; 95% confidence interval [CI] = -0.03, 0.17 pg/mL; P = 0.190; WMD =0.05 pg/mL; 95% CI = -0.01, 0.12 pg/mL; P = 0.092; respectively). In subgroup analysis, soy isoflavones plus soy protein could increase the serum concentration of IL-6 in studies with soy isoflavones dose ≤87 mg/days, cross-over design, weak quality, and studies on participants who had health risk factors or diseases. The serum concentration of TNF-α increased in studies with cross-over design, intervention duration ≤56 days, and body mass index (BMI) >27, and in studies that were conducted on at-risk or sick participants. In conclusion, our meta-analysis did not confirm any significant effect on serum concentration of IL-6 and TNF-α among post-menopausal women.
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2.
IL-6 antagonists to replace systemic corticosteroids as the preferred anti-inflammatory therapy in patients with COVID-19?
Kow, CS, Zaihan, AF, Ramachandram, DS, Hasan, SS
Cytokine. 2022;:155730
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3.
The Association between Interleukin-6 Gene Polymorphisms and Risk of Systemic Lupus Erythematosus: A Meta-analysis with Trial Sequential Analysis.
Liu, J, Liao, MQ, Cao, DF, Yang, Y, Yang, Y, Liu, YH, Zeng, FF, Chen, XH
Immunological investigations. 2021;(2-3):259-272
Abstract
BACKGROUND Molecular epidemiological studies have sought associations between interleukin-6 (IL-6) polymorphisms and the risk of systemic lupus erythematosus (SLE); however, the results are controversial. Therefore, we conducted a meta-analysis with trial sequential analysis to evaluate a more accurate estimation of the associations. METHODS Published literatures reporting the relationships of two IL-6 polymorphisms (G-174C and G-572C) and SLE risk were retrieved from electronic databases such as PubMed and EMBASE. The most appropriate genetic model was chosen for each polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Trial sequential analysis (TSA) was introduced to assess the information size and the positive results. RESULTS With 17 studies (2780 cases and 3100 controls) included, a dominant association (CC+GC vs. GG) was suggested for G-174C polymorphism, and compared with the GG genotype, the CC+GC genotype of G-174C was associated with a decreased SLE risk (OR = 0.71; 95% CI = 0.56-0.88, P =.02). No association was found for G-572C under all genetic models (e.g. OR and 95%CI for CC+GC vs. GG: 0.89, 0.73-1.08, P =.22). Subgroup analyses indicated that SLE risk decreased in G-174C polymorphism by subgroups of Caucasian population, publications after 2010, studies with high quality, and studies complied with Hardy-Weinberg equilibrium (HWE). TSA suggested that the sample sizes used for G-572C were insufficient. CONCLUSION We found that the minor allele C of IL6G-174C polymorphism is a protective factor in SLE. Further studies with a larger sample size are needed to confirm the null association for G-572C.
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4.
Can soy isoflavones plus soy protein change serum levels of interlukin-6? A systematic review and meta-analysis of randomized controlled trials.
Gholami, A, Baradaran, HR, Hariri, M
Phytotherapy research : PTR. 2021;(3):1147-1162
Abstract
In the present review, we aimed to summarize the effect of soy isoflavones plus soy protein on circulating interlukin-6 (IL-6) in adult participants. Databases including ISI Web of Science, PubMed, Scopus, Cochrane Library, and clinicaltrials.gov were searched up to 23 March 2020. The mean change from baseline of IL-6 concentrations and its SD for intervention and comparison groups were used to calculate the effect size. If the heterogeneity test was statistically significant, DerSimonian and Laird random effects model was used. Cochran's Q test and I-squared statistic were also used to compute the statistical heterogeneity of the intervention's effects. Eighteen studies were known to be eligible for systematic review and 14 studies were selected for meta-analysis. Our meta-analysis results indicated a non-significant effect in serum IL-6 concentrations compared to the comparison group (WMD = 0.03 pg/ml, 95% CI: -0.06, 0.12; p = .459). In subgroup analysis, based on soy isoflavones dosage, it was observed that this combination could reduce IL-6 levels in studies that used isoflavones with dose >84 mg/day (WMD = -0.12 pg/ml 95% CI: -0.24, -0.004; p = .042, I2 = 82.7%) and in articles with a good quality (WMD = -0.15 pg/ml 95% CI: -0.24, -0.05; p = .003, I2 = 62.3%). Performing well-designed intervention studies using a high dose of soy isoflavones is recommended to confirm the beneficial effects of soy ingredients on IL-6.
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5.
The effect of exercise intensity on chronic inflammation: A systematic review and meta-analysis.
Rose, GL, Skinner, TL, Mielke, GI, Schaumberg, MA
Journal of science and medicine in sport. 2021;(4):345-351
Abstract
OBJECTIVES Chronic inflammation is independently associated with the incidence and progression of chronic disease. Exercise has been found to reduce chronic inflammation, however the role of exercise intensity (work rate) is unknown. This review aimed to determine the pooled effect of higher- compared to lower-intensity aerobic and resistance exercise on chronic inflammation in adults. DESIGN Systematic review and meta-analysis. METHODS Five electronic databases were searched. Intervention trials that assessed the effect of ≥2 different exercise intensities on peripheral markers of chronic inflammation [c-reactive protein (CRP), interleukin (IL)-6, tumour necrosis factor (TNF)-α and IL-10] in adults were included. Random-effect meta-analyses were conducted to calculate the mean difference in change scores between groups [effect size (ES)]. Sub-group analyses were performed to explore the influence of age, chronic disease, body mass index and intervention duration on inflammation heterogeneity. RESULTS Of 3952 studies identified, 27 were included. There were no significant effects of exercise intensity on IL-6 (ES=-0.039, 95%CI=-0.353-0.275; p=0.806), TNF-α (ES=0.296, 95%CI=-0.184-0.777; p=0.227) and IL-10 (ES=0.007, 95%CI=-0.904-0.919; p=0.987). A significant pooled ES was observed for higher- versus lower-intensity exercise on CRP concentrations, in studies of middle-aged adults (ES=-0.412, 95%CI=-0.821- -0.004, p=0.048) or interventions >9 weeks in duration (ES=-0.520, 95%CI=-0.882--0.159, p=0.005). CONCLUSIONS Exercise intensity did not influence chronic inflammatory response. However, sub-analyses suggest that higher-intensity training may be more efficacious than lower-intensity for middle-aged adults, or when longer duration interventions are implemented (>9 weeks), in the most commonly-reported analyte (CRP).
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6.
Anti-interleukin-6 therapies for Covid-19: A systematic review, critical appraisal and meta-analysis.
Elavarasi, A, Sahoo, RK, Seth, T, Shalimar, , Madan, K, Nischal, N, Soneja, M, Sharma, A, Garg, P, Prasad, K
The National medical journal of India. 2020;(3):152-157
Abstract
BACKGROUND . Coronavirus disease 2019 (Covid-19) has emerged as a pandemic by end-January 2020. Of the infected patients, 10%-15% may develop severe or critical illness. So far, no definite treatment is available for Covid-19. Cytokine release syndrome may underlie the pathogenesis of severe and critical disease. Anti-interleukin (IL)-6 therapies are being tried to improve clinical outcomes. METHODS . We did a systematic review to identify the available literature on anti-IL-6 therapies in the treatment of Covid-19 and used the GRADE method to assess the quality of evidence. RESULTS . Four case series and 10 case reports were identified. On critical assessment, we found that these studies reported some beneficial effect of anti-IL-6 therapy, but all the studies had a high risk of bias. The pooled estimate showed that 42% of patients improved but with a very wide confidence interval (CI) (95% CI 1%-91%) and substantial heterogeneity (I2 = 95%). The overall quality of evidence was graded as 'very low'. CONCLUSIONS . Although promising, anti-IL-6 therapy for Covid-19 needs to be tested in randomized controlled trials to provide robust evidence.
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7.
Association between diabetic retinopathy and interleukin-related gene polymorphisms: a machine learning aided meta-analysis.
Sun, X, Guo, S
Ophthalmic genetics. 2020;(3):216-222
Abstract
BACKGROUND Diabetic retinopathy (DR) is a severe complication of diabetes and a common cause of visual loss in adults. We aimed to assess the correlation between IL gene-related SNPs and the incidence of DR and attempted to predict DR with combined mutation site detection. METHODS A systematic search of databases was performed up to August 2019. Five genetic models were used to analyze associations. Machine learning methods were implemented to improve SNP-related disease prediction. RESULTS Sixteen trials assessing a total of 7221 patients were included in our meta-analysis. IL6/rs1800795, rs1800796, and IL10/rs1800896 were analyzed. For the IL-6 gene, there was no significant association between rs1800795 and the incidence of DR (allelic model: OR, 1.091; 95% CI, 0.892-1.334; p = .396). There was no significant correlation between rs1800796 (allelic model: OR, 1.135; 95% CI, 0.678-1.901; p = .63), rs1800896 (allelic model: OR, 1.047; 95% CI, 0.788-1.392; p = .752) and the incidence of DR. Unfortunately, the machine learning results also showed that the combined detection of two SNPs could not accurately predict DR occurrence. CONCLUSION rs1800795 and rs1800796 in the IL-6 gene and rs1800896 in IL-10 gene are not related to the incidence of DR. Mutations in multiple SNPs for each DR patient still need to be specifically assessed to increase prediction accuracy.
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8.
The effects of soy supplementation on inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials.
Asbaghi, O, Yaghubi, E, Nazarian, B, Kelishadi, MR, Khadem, H, Moodi, V, Naeini, F, Ghaedi, E
Cytokine. 2020;:155282
Abstract
BACKGROUND Soy products contain several compounds with anti-inflammatory properties like genistein and daidzein which reported to act through different pathways. Present study conducted considering the inconsistent results and lack of any comprehensive review regarding randomized controlled trials which assess the effect of soy products on inflammatory markers. METHODS Following electronic databases were searched up to March 2020: PubMed, Scopus, ISI web of science, and Cochrane Library All randomized trials which assessed the effect of soy product supplementation on c-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were included for last analysis. Treatment effects were expressed as mean difference (MD) and the standard deviation (SD) of outcomes. To estimate the overall effect the random-effects model was employed. RESULTS Finally, 51 randomized trial were included for present study. Last analysis showed that soy product supplementation lead to significant reduction in CRP (MD -0.27 mg/L; 95% CI: -0.51, -0.02, p = 0.028) but it did not affect IL-6 (MD 0.0 pg/ml; 95% CI: -0.06, 0.06, p = 0.970) and TNF-α (MD = -0.04 pg/ml; 95% CI: -0.11, 0.03, p = 0.252). Subgroup analysis showed that soy supplementation had a significant impact on decreasing IL-6 and TNF-α levels when studies had a long-term intervention (≥12 weeks) and used low dose isoflavone (<100 mg/day). CONCLUSION In conclusion, present systematic review and meta-analysis found a significant reduction in CRP levels after soy supplementation whiles IL-6 and TNF-α did not affect.
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9.
The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis.
Ulhaq, ZS, Soraya, GV, Budu, , Wulandari, LR
Scientific reports. 2020;(1):17453
Abstract
Interleukin-6 (IL-6) is one of the key regulators behind the inflammatory and pathological process associated with ophthalmic diseases. The role of IL-6-174 G/C polymorphism as well as intraocular IL-6 levels among various eye disease patients differ across studies and has not been systematically reviewed. Thus, this study aims to provide a summary to understand the relationship between IL-6 and ophthalmic disease. In total, 8,252 and 11,014 subjects for IL-6-174 G/C and intraocular levels of IL-6, respectively, were retrieved from PubMed, Scopus and Web of Science. No association was found between IL-6-174 G/C polymorphisms with ocular diseases. Subgroup analyses revealed a suggestive association between the GC genotype of IL-6-174 G/C with proliferative diabetic retinopathy (PDR). Further, the level of intraocular IL-6 among ocular disease patients in general was found to be higher than the control group [standardized mean difference (SMD) = 1.41, 95% confidence interval (CI) 1.24-1.58, P < 0.00001]. Closer examination through subgroup analyses yielded similar results in several ocular diseases. This study thus indicates that the IL-6-174 G/C polymorphism does not predispose patients to ocular disease, although the GC genotype is likely to be a genetic biomarker for PDR. Moreover, intraocular IL-6 concentrations are related to the specific manifestations of the ophthalmic diseases. Further studies with larger sample sizes are warranted to confirm this conclusion.
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10.
The association of interieukin-6 polymorphism (rs1800795) with microvascular complications in Type 2 diabetes mellitus.
Cui, J, Zhang, X, Guo, C, Zhang, L
Bioscience reports. 2020;(10)
Abstract
OBJECTIVES To evaluate the effects of the single-nucleotide polymorphism (SNP) rs1800795 in interieukin-6 (IL-6) gene on diabetic microvascular complications of Type 2 diabetes mellitus (T2DM), using statistical meta-analysis. METHODS Literature pertaining to the relationship between the SNP rs1800795 and microvascular complications of T2DM including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and foot disease was retrieved from PubMed, Web of Science Knowledge and SinoMed databases. Original information was analyzed using Stata 12.0, including meta-analysis statistics, test for heterogeneity, evaluation of publication bias and sensitivity. Subgroup analysis was conducted to assess the effect of specific factors on the corresponding results. RESULTS In total, 14 eligible articles were obtained. The SNP rs1800795 in IL-6 gene is not correlated with risk of microvascular complications in T2DM. Among the original literature, a genetic model (OR = 1.071, 95% CI: 0.681-1.685, P=0.767), an allelic genetic model (OR = 1.010, 95% CI: 0.959-1.063, P=0.703), a heterozygote genetic model (OR = 1.107, 95% CI: 0.916-1.339, P=0.292), a dominant genetic model (OR = 1.108, 95% CI: 0.885-1.387, P=0.372), and a recessive genetic model (OR = 0.978, 95% CI: 0.646-1.478, P=0.917) were included respectively. In the subgroup analysis by types of diabetic microvascular complications, we found no correlation between the SNP rs1000795 polymorphism and complications of T2DM in either the homozygote genetic model or the allelic genetic model (P<0.05). CONCLUSION Our results demonstrate that rs1800795 polymorphism in IL-6 gene is not correlated with the susceptibility of microvascular complications of T2DM.