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Sodium butyrate is well-known for its immune-modulatory properties. Studies until now only focused on the in vitro effects of butyrate or assessed local effects in the gut upon butyrate administration. In this trial, we studied the systemic anti-inflammatory effects induced by sodium butyrate supplementation in humans. Nine healthy (Lean) and ten obese (metabolic syndrome group, MetSyn) males were given 4 grams sodium butyrate daily for 4 weeks. PBMCs were isolated before and after supplementation for direct stimulation experiments and induction of trained immunity by oxidized low-density lipoprotein (oxLDL), β-glucan, or Bacillus Calmette-Guérin vaccine (BCG). Butyrate supplementation moderately affected some of the cytokine responses in the MetSyn group. In the direct stimulation setup, effects of butyrate supplementation were limited. Interestingly, butyrate supplementation decreased oxLDL-induced trained immunity in the MetSyn group for LPS-induced IL-6 responses and Pam3CSK4-induced TNF-α responses. Induction of trained immunity by β-glucan was decreased by butyrate in the MetSyn group for Pam3CSK4-induced IL-10 production. In this study, while having only limited effects on the direct stimulation of cytokine production, butyrate supplementation significantly affected trained immunity in monocytes of obese individuals with metabolic complications. Therefore, oral butyrate supplementation may be beneficial in reducing the overall inflammatory status of circulating monocytes in patients with metabolic syndrome. [ABSTRACT FROM AUTHOR]

About 60% of RA patients don’t achieve good response with biological disease-modifying anti-rheumatic drugs bDMARD treatment (including TNF inhibitors, TNFi’s). Previously, a link between TNFα and interleukin (IL)-32 was reported in RA. However, the exact mechanism linking IL-32 to response to treatment as not been studied yet. Therefore, we explored the influence of a promoter single nucleotide polymorphism (SNP) rs4786370 in IL-32 on clinical responsiveness to TNFi’s in RA patients, potentially serving as new biomarker in RA. Expression of pro-inflammatory cytokines by peripheral mononuclear cells (PBMCs) from RA patients and healthy individuals were studied. Moreover, “ex vivo response” and clinical response to anti-TNFα therapy (etanercept, adalimumab) were measured and stratified for the IL-32 SNP. Higher IL-32 protein production was observed in RA patients. Additionally, patients bearing the CC genotype showed higher IL-32 protein and cytokine expression. DAS28 was independent of the promoter SNP, however, the “ex vivo” cytokine response was not. IL-32 mRNA and protein production was higher in RA patients, with a trend towards higher concentrations in patients bearing the CC genotype. Furthermore, genotype dependent IL-1 beta production might predict clinical response to etanercept/adalimumab. This indicates that IL-32 could play a role in predicting response to treatment in RA. [ABSTRACT FROM AUTHOR]