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It is recognised that ageing induces various changes to the human colonic microbiota. Most relevant is a reduction in bifidobacteria, which is a health-positive genus. Prebiotics, such as galacto-oligosaccharides (GOS), are dietary ingredients that selectively fortify beneficial gut microbial groups. Therefore, they have the potential to reverse the age-related decline in bifidobacteria and modulate associated health parameters. We assessed the effect of GOS mixture (Bimuno (B-GOS)) on gut microbiota, markers of immune function and metabolites in forty elderly (age 65–80 years) volunteers in a randomised, double-blind, placebo (maltodextrin)-controlled, cross-over study. The intervention periods consisted of 10 weeks with daily doses of 5·5 g/d with a 4-week washout period in between. Blood and faecal samples were collected for the analyses of faecal bacterial populations and immune and metabolic biomarkers. B-GOS consumption led to significant increases in bacteroides and bifidobacteria, the latter correlating with increased lactic acid in faecal waters. Higher IL-10, IL-8, natural killer cell activity and C-reactive protein and lower IL-1β were also observed. Administration of B-GOS to elderly volunteers may be useful in positively affecting the microbiota and some markers of immune function associated with ageing.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease in which the gut microbiota is altered. Probiotics are microorganisms that can normalize gut microbiota; thus, they may help to alleviate RA symptoms. The objective of the present clinical trial was to assess the effects of probiotic supplementation on disease activity and inflammatory cytokines in patients with RA. Forty-six patients with RA were assigned into two groups in this randomized, double-blind, placebo-controlled clinical trial. The patients in the probiotic group received a daily capsule that contained a minimum of 108 colony-forming units of Lactobacillus casei 01 for 8 wk. The placebo group took capsules filled with maltodextrin for the same time period. Questionnaires, anthropometric measurements, and fasting blood samples were collected, and the participants were assessed by a rheumatologist at baseline and at the end of the trial. Disease activity score was significantly decreased by the intervention, and there was a significant difference between the two groups at the end of the study (P < 0.01). Three of the assessed serum proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-12) significantly decreased in the probiotic group (P < 0.05); however, serum levels of interleukin-1 β were not significantly affected by the probiotic (P = 0.22). The serum level of regulatory cytokine (interleukin-10) was increased by the supplementation (P < 0.05). The proportion of interleukin-10 to interleukin-12 was significantly increased in the probiotic group as well. L. casei 01 supplementation improved the disease activity and inflammatory status of patients with RA. Further studies are warranted to confirm these results, and such confirmation may lead to the introduction of probiotics as adjunctive therapy for this population.

Previous research have implicated critical roles of systemic inflammation in the development of Multiple Sclerosis (MS). But the causal relationship between interleukins (ILs) and MS has not been fully elucidated. In this study, we applied Mendelian randomization (MR) approaches to address the causal associations between genetically determined circulating levels of ILs and the risk of MS. Genetic instruments for circulating IL-1 receptor antagonist (IL-1Ra), IL-2 receptor α subunit (IL-2Rα), IL-6, IL-16, IL-17, and IL-18 were obtained from recently published genome-wide association studies (GWAS). Summary-level data for MS were obtained from the International Multiple Sclerosis Genetics Consortium. MR analyses were performed using the R software (version 3.6.1, The R Foundation) and the TwoSampleMR package. Genetic predisposition to higher circulating levels of IL-2Rα were significantly associated with MS risk. The odds ratio (OR) was 1.22 (95% confidence interval [CI], 1.12-1.32; < 0.001) per one standard deviation increase in circulating IL-2Rα levels. There was a suggestive association of circulating IL-1Ra with MS risk (OR, 0.94; 95% CI, 0.88-0.99; = 0.027). The other ILs were not associated with the outcome. Our results indicated that circulating IL-2Rα was causally associated with risk of MS.

Patients with cystic fibrosis (CF) suffer from chronic lung infection and inflammation leading to respiratory failure. Vitamin D deficiency is common in patients with CF, and correction of vitamin D deficiency may improve innate immunity and reduce inflammation in patients with CF. We conducted a double-blinded, placebo-controlled, randomized clinical trial of high-dose vitamin D to assess the impact of vitamin D therapy on antimicrobial peptide concentrations and markers of inflammation. We randomized 30 adults with CF hospitalized with a pulmonary exacerbation to 250 000 IU of cholecalciferol or placebo, and evaluated changes in plasma concentrations of inflammatory markers and the antimicrobial peptide LL-37 at baseline and 12 weeks post intervention. In the vitamin D group, there was a 50.4% reduction in tumor necrosis factor-α (TNF-α) at 12 weeks ( P <0.01), and there was a trend for a 64.5% reduction in interleukin-6 (IL-6) ( P =0.09). There were no significant changes in IL-1β, IL-8, IL-10, IL-18BP and NGAL (neutrophil gelatinase-associated lipocalin). We conclude that a large bolus dose of vitamin D is associated with reductions in two inflammatory cytokines, IL-6 and TNF-α. This study supports the concept that vitamin D may help regulate inflammation in CF, and that further research is needed to elucidate the potential mechanisms involved and the impact on clinical outcomes.

Background The IABP-SHOCK-trial was a morbidity-based randomized controlled trial in patients with infarction-related cardiogenic shock (CS), which used the change of the quantified degree of multiorgan failure as determined by APACHE II score over a 4-day period as primary outcome measure. The prospective hypothesis was that adding IABP therapy to “standard care” would improve CS-triggered multi organ dysfunction syndrome (MODS). The primary endpoint showed no difference between conventionally managed cardiogenic shock patients and those with IABP support. In an inflammatory marker substudy, we analysed the prognostic value of interleukin (IL)-1β, -6, -7, -8, and -10 in patients with acute myocardial infarction complicated by cardiogenic shock. Design Inflammatory marker substudy of the prospective, randomized, controlled, open label IABP-SHOCK-trial (Clinical-Trials-gov-ID-NCT00469248). Setting and methods A single-center study was performed in a 12-bed Intensive-Care-Unit in an university hospital in which 40 consecutive patients were enrolled with an observational period of 96 h. Results The pro- and anti-inflammatory markers IL-6, -7, -8 and -10 showed a predictive power for mortality of infarct-related CS patients, while IL-1β did not discriminate. The maximal values during the observational period, in case of IL-7 the minimal value, showed the best power to predict mortality. Both, ROC and multivariate analyses confirmed these suggestions (area under the curve: IL-8, 0.80 ± 0.08; IL-6, 0.79 ± 0.08; IL-10, 0.76 ± 0.08; IL-7, 0.69 ± 0.08). Inflammatory markers were not affected by the presence of IABP support. Conclusion The inflammatory response in patients with myocardial infarction complicated by cardiogenic shock, as reflected by the inflammatory markers IL-6, IL-7, IL-8 and IL-10, demonstrates a clinically relevant prognostic contribution to clinical outcome.

Background Up to 80% of breast cancer patients suffer from Cancer Related Cognitive Impairments (CRCI). Exercise is suggested as a potential supportive care option to reduce cognitive decline in cancer patients. This study will investigate the effects of a high-intensity interval endurance training (HIIT) on CRCI in breast cancer patients. Potentially underlying immunological and neurobiological mechanisms, as well as effects on patients’ self-perceived cognitive functioning and common cancer related side-effects, will be explored. Methods A single-blinded randomized controlled trial will be carried out. The impact of HIIT on CRCI will be compared to that of a placebo-intervention (supervised myofascial release training). Both interventions will be conducted simultaneously with the patients’ first-line chemotherapy treatment typically lasting 12–18 weeks. Fifty-nine women with breast cancer will be included in each of the two groups. The study is powered to detect (α = .05, β = .2) a medium effect size difference between the two groups (d = .5) in terms of patients’ change in cognitive testing performances, from baseline until the end of the exercise-intervention. The cognitive test battery, recommended by the International Cancer and Cognition Task Force to assess CRCI, will be used as primary measure. This includes the Hopkins Verbal Learning Test (learning/verbal memory), the Controlled Oral Word Association Test (verbal fluency) and the Trail-Making-Test A/B (attention/set-switching). The following endpoints will be assessed as secondary measures: Go-/No-Go test performance (response inhibition), self-perceived cognitive functioning, serum levels of pro- and antiinflammatory markers (tumor necrosis factor alpha, Interleukin-6, Interleukin-1 alpha, Interleukin-1 beta, C-reactive protein, Interleukin-1 receptor antagonist and Interleukin-10), serum levels of neurotrophic and growth factors (brain-derived neurotrophic factor, insulin-like growth factor 1 and vascular endothelial growth factor), as well as common cancer-related side effects (decrease in physical capacity, fatigue, anxiety and depression, sleep disturbances, quality of life and chemotherapy compliance). Discussion This study will provide data on the question whether HIIT is an effective supportive therapy that alleviates CRCI in breast cancer patients. Moreover, the present study will help shed light on the underlying mechanisms of potential CRCI improving effects of exercise in breast cancer patients. Trial registration DRKS.de, German Clinical Trials Register (DRKS), ID: DRKS00011390 , Registered on 17 January 2018.

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17) response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases.

Background/Aims: The primary therapeutic goals in ulcerative colitis (UC) are to maintain excellent quality of life (QOL) by treating flare-ups when they occur, and preventing flare-ups. Since stress can trigger UC flare-ups, we investigated the efficacy of mindfulness-based stress reduction (MBSR) to reduce flare-ups and improve QOL. Methods: Patients with moderately severe UC, in remission, were randomized to MBSR or time/attention control. Primary outcome was disease status. Secondary outcomes were changes in markers of inflammation and disease activity, markers of stress and psychological assessments. Results: 55 subjects were randomized. Absence of flares, time to flare and severity of flare over 1 year were similar between the two groups. However, post hoc analysis showed that MBSR decreased the proportion of participants with at least one flare-up among those with top tertile urinary cortisol and baseline perceived stress (30 vs. 70%; p < 0.001). MBSR patients who flared demonstrated significantly lower stress at the last visit compared to flared patients in the control group (p = 0.04). Furthermore, MBSR prevented a drop in the Inflammatory Bowel Disease Quality of Life Questionnaire during flare (p < 0.01). Conclusion: MBSR did not affect the rate or severity of flare-ups in UC patients in remission. However, MBSR might be effective for those with high stress reactivity (high perceived stress and urinary cortisol) during remission. MBSR appears to improve QOL in UC patients by minimizing the negative impact of flare-ups on QOL. Further studies are needed to identify a subset of patients for whom MBSR could alter disease course.

Background/Objectives: Probiotics are defined as ‘living micro-organisms that when administered in adequate amounts confer a health benefit to the host’. Different probiotic strains have been investigated for beneficial effects on allergic disorders. The purpose of the current study was to evaluate the effect of orally administering the probiotic Nestlé culture collection (NCC)2818 Bifidobacterium lactis strain on immune parameters and nasal symptom scores in subjects suffering from seasonal allergic rhinitis (SAR). Subjects/Methods: The study was a double-blinded, parallel, randomized placebo-controlled trial conducted during the peak of the pollen season. Adult subjects with clinical history of SAR and positive skin prick test to grass pollen were recruited. The subjects received B. lactis NCC2818 or placebo for 8 weeks and completed symptom questionnaires every week. Whole blood was collected at baseline (V1), 4 weeks (V2) and 8 weeks (V3) to measure immune parameters. Results: Concentrations of Th-2 cytokines, secreted by stimulated blood lymphocytes, were significantly lower in the probiotic group compared with the placebo group at V3 (interleukin (IL)-5, P =0.016; IL-13, P =0.005). Total nasal symptom scores were significantly lower in the second month of the study (weeks 5–8) in the probiotic group compared with the placebo group ( P =0.03). Also, percentages of activated CD63 expressing basophils were significantly lower in the probiotic group at V2 ( P =0.02). Conclusions: Oral administration of the probiotic NCC2818 mitigates immune parameters and allergic symptoms during seasonal exposure. These promising results warrant that B. lactis NCC2818 be investigated further in large-scale trials for management of respiratory allergy.

Background An acute bout of exercise induces an inflammatory response characterized by increases in several cytokines. Caffeine ingestion could modify this inflammatory response. The aim of this study was to determine the effects of caffeine supplementation on plasma levels of cytokines, mainly IL-10 and IL-6, in response to exercise. Methods In a randomized, crossover, double-blinded study design, thirteen healthy, well-trained recreational male athletes performed, on two different occasions, a treadmill exercise test (60 min at 70% VO 2 max) after ingesting 6 mg/kg body mass of caffeine or placebo. Blood samples were taken before exercising, immediately after finishing and 2 h after finishing the exercise. Plasma concentrations of IL-10, IL-6, IL-1β, IL-1ra, IL-4, IL-8, IL-12 and IFN-γ, adrenaline, cortisol and cyclic adenosine monophosphate (cAMP) were determined. The capacity of whole blood cultures to produce cytokines in response to endotoxin (LPS) was also determined. Changes in blood variables were analyzed using a time (pre-exercise, post-exercise, recovery) x condition (caffeine, placebo) within-between subjects ANOVA with repeated measures. Results Caffeine supplementation induced higher adrenaline levels in the supplemented participants after exercise (257.3 ± 53.2 vs. 134.0 ± 25.7 pg·mL − 1 , p  = 0.03) and higher cortisol levels after recovery (46.4 ± 8.5 vs. 32.3 ± 5.6 pg·mL − 1 , p  = 0.007), but it did not influence plasma cAMP levels ( p  = 0.327). The exercise test induced significant increases in IL-10, IL-6, IL-1ra, IL-4, IL-8, IL-12 and IFN-γ plasma levels, with IL-6 and IL-10 levels remaining high after recovery. Caffeine supplementation influenced only IL-6 (3.04 ± 0.40 vs. 3.89 ± 0.62 pg·mL − 1 , p  = 0.003) and IL-10 (2.42 ± 0.54 vs. 3.47 ± 0.72 pg·mL − 1 , p  = 0.01) levels, with higher concentrations after exercise in the supplemented condition. No effect of caffeine was observed on the in vitro stimulated cytokine production. Conclusions The results of the present study indicate a significant influence of caffeine supplementation increasing the response to exercise of two essential cytokines such as IL-6 and IL-10. However, caffeine did not influence changes in the plasma levels of other cytokines measured and the in vitro-stimulated cytokine production.