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1.
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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Beneficial effects of novel aureobasidium pullulans strains produced beta-1,3-1,6 glucans on interleukin-6 and D-dimer levels in COVID-19 patients; results of a randomized multiple-arm pilot clinical study.
Raghavan, K, Dedeepiya, VD, Suryaprakash, V, Rao, KS, Ikewaki, N, Sonoda, T, Levy, GA, Iwasaki, M, Senthilkumar, R, Preethy, S, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112243
Abstract
OBJECTIVE In this pilot clinical study, we report the beneficial effects of beta glucans derived from two strains AFO-202 and N-163 of a black yeast Aureobasidium pullulans on the biomarkers for cytokine storm and coagulopathy in COVID-19 patients. METHODS A total of 24 RT-PCR positive COVID-19 patients were recruited and randomly divided into three groups (Gr): Gr. 1 control (n = 8) - Standard treatment; Gr. 2: Standard treatment + AFO-202 beta glucan (n = 8); and Gr. 3, Standard treatment + combination of AFO-202 and N-163 beta glucans (n = 8) for 30 days. RESULTS There was no mortality or requirement of ventilation of the subjects in any of the groups. There was a decrease in D-Dimer values (751 ng/ml to 143.89 ng/ml) and IL-6 values (7.395-3.16 pg/ml) in Gr. 1 in 15 days but the levels increased to abnormal levels on day 30 (D-Dimer: 202.5 ng/ml; IL-6 55.37 pg/ml); which steadily decreased up to day 30 in groups 2 (D-dimer: 560.99 ng/dl to 79.615; IL-6: 26.18-3.41 pg/ml) and 3 (D-dimer: 1614 ng/dl to 164.25 ng/dl; IL-6: 6.25-0.5 pg/ml). The same trend was observed with ESR. LCR and LeCR increased while NLR decreased significantly in Gr. 3. CD4 + and CD8 + T cell count showed relatively higher increase in Gr.3. There was no difference in CRP within the groups. CONCLUSION As these beta glucans are well known food supplements with a track record for safety, larger multi-centric clinical studies are recommended to validate their use as an adjunct in the management of COVID-19 and the ensuing long COVID-19 syndrome.
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Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial.
Öcal, O, Schütte, K, Kupčinskas, J, Morkunas, E, Jurkeviciute, G, de Toni, EN, Ben Khaled, N, Berg, T, Malfertheiner, P, Klümpen, HJ, et al
Journal of cancer research and clinical oncology. 2022;(2):475-485
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Abstract
PURPOSE To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib. METHODS A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response. RESULTS Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9-8.9], p < 0.001) and IL-8 (HR, 2.4 [1.2-4.7], p = 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22-7.3], p = 0.017) and IL-8 (HR, 2.19 [1.02-4.7], p = 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%, p = 0.007; IL-8, 50.0% vs. 17.4%, p = 0.011). CONCLUSION IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.
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Whole Grain Consumption and Inflammatory Markers: A Systematic Literature Review of Randomized Control Trials.
Milesi, G, Rangan, A, Grafenauer, S
Nutrients. 2022;(2)
Abstract
Whole grain foods are rich in nutrients, dietary fibre, a range of antioxidants, and phytochemicals, and may have potential to act in an anti-inflammatory manner, which could help impact chronic disease risk. This systematic literature review aimed to examine the specific effects of whole grains on selected inflammatory markers from human clinical trials in adults. As per the Preferred Reporting Items for Systematic Reviews (PRISMA) protocol, the online databases MEDLINE, Embase, Cochrane, CINAHL, and Scopus were searched from inception through to 31 August 2021. Randomized control trials (RCTs) ≥ 4 weeks in duration, reporting ≥1 of the following: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF), were included. A total of 31 RCTs were included, of which 16 studies recruited overweight/obese individuals, 12 had pre-existing conditions, two were in a healthy population, and one study included participants with prostate cancer. Of these 31 RCTs, three included studies with two intervention arms. A total of 32 individual studies measured CRP (10/32 were significant), 18 individual studies measured IL-6 (2/18 were significant), and 13 individual studies measured TNF (5/13 were significant). Most often, the overweight/obese population and those with pre-existing conditions showed significant reductions in inflammatory markers, mainly CRP (34% of studies). Overall, consumption of whole grain foods had a significant effect in reducing at least one inflammatory marker as demonstrated in 12/31 RCTs.
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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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Expression of NF-κB, IL-6, and IL-10 genes, body composition, and hepatic fibrosis in obese patients with NAFLD-Combined effects of oleoylethanolamide supplementation and calorie restriction: A triple-blind randomized controlled clinical trial.
Tutunchi, H, Ostadrahimi, A, Saghafi-Asl, M, Roshanravan, N, Shakeri-Bavil, A, Asghari-Jafarabadi, M, Farrin, N, Mobasseri, M
Journal of cellular physiology. 2021;(1):417-426
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common noncommunicable diseases worldwide. The present study aimed to investigate the effects of oleoylethanolamide (OEA) supplementation combined with calorie restriction on inflammation, body composition, and hepatic fibrosis among obese patients with NAFLD. In this 12-week randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group. The weight-loss diet was also designed for both groups. Pre- and postintervention messenger RNA expression levels of the transcription factor nuclear factor-κB (NF-κB), interleukin-6 (IL-6) and IL-10, body composition, and NAFLD fibrosis score were assessed. At the end of the study, the OEA group showed lower NF-κB and IL-6 expression levels compared to the placebo (p < .01). However, IL-10 expression level was approximately twofold higher in the OEA group compared to the placebo group (p = .008). A significant reduction was observed in the fat mass of the OEA group compared to the placebo (p = .044) postintervention. In addition, OEA supplementation led to a significant increase in fat-free mass in the OEA group compared to the placebo (p = .032). A remarkable increase was observed in resting metabolic rate (RMR) in the OEA group (p = .009); however, it was not found in the placebo group. There were no significant between-group differences in RMR postintervention. In addition, no significant within-and between-group differences were observed in the NAFLD fibrosis score at the end of the trial. Treatment with OEA along with weight-loss intervention could significantly improve inflammation and body composition in patients with NAFLD.
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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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A prospective observational study of urinary cytokines and inflammatory response in patients with Overactive Bladder Syndrome.
Gill, K, Horsley, H, Swamy, S, Khasriya, R, Malone-Lee, J
BMC urology. 2021;(1):39
Abstract
BACKGROUND Contemporary studies have discredited the methods used to exclude urinary tract infection (UTI) when treating overactive bladder (OAB). Thus we must revisit the OAB phenotype to check that UTI has not been overlooked. AIMS To examine the differences in urinary cytokines IL6 and lactoferrin in OAB patients compared to controls, with references to microscopy of urine and enhanced quantitative urine culture. METHODS A blinded, prospective cohort study with normal controls using six repeated measures, achieved two-monthly, over 12 months. RESULTS The differences between patients and controls in urine IL6 (F = 49.0, p < .001) and lactoferrin (F = 228.5, p < .001) were significant and of a magnitude to have clinical implications. These differences were for lactoferrin correlated to symptoms (9.3, p = .003); for both to pyuria (IL6 F = 66.2, p < .001, Lactoferrin F = 73.9, p < .001); and for IL6 microbial abundance (F = 5.1, p = .024). The pathological markers had been missed by urinary dipsticks and routine MSU culture. CONCLUSION The OAB phenotype may encompass patients with UTI that is being overlooked because of the failure of standard screening methods.
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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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Poor Masticatory Capacity and Blood Biomarkers of Elevated Cardiovascular Disease Risk in the Community: The Paris Prospective Study III.
Chatzopoulou, E, Rangé, H, Deraz, O, Boutouyrie, P, Perier, MC, Guibout, C, Thomas, F, Andrieu, M, Bailly, K, Vedie, B, et al
Arteriosclerosis, thrombosis, and vascular biology. 2021;(7):2225-2232
Abstract
[Figure: see text].