Anti-Inflammatory Effect of Caffeine on Muscle under Lipopolysaccharide-Induced Inflammation.

Evidence has shown that caffeine administration reduces pro-inflammatory biomarkers, delaying fatigue and improving endurance performance. This study examined the effects of caffeine administration on the expression of inflammatory-, adenosine receptor- (the targets of caffeine), epigenetic-, and oxidative metabolism-linked genes in the muscle of mice submitted to lipopolysaccharide (LPS)-induced inflammation. We showed that caffeine pre-treatment before LPS administration reduced the expression of , , and , and increased and . The negative modulation of the inflammatory response induced by caffeine involved the reduction of inflammasome components, and , promoting an anti-inflammatory scenario. Caffeine treatment promoted the upregulation of adenosinergic receptors, and , an effect that was counterbalanced by LPS. Moreover, there was observed a marked promoter hypermethylation, which could represent a compensatory response towards the increased expression. Though caffeine administration did not alter DNA methylation patterns, the expression of DNA demethylating enzymes, and , was increased in mice receiving Caffeine+LPS, when compared with the basal condition. Finally, caffeine administration attenuated the LPS-induced catabolic state, by rescuing basal levels of expression. Altogether, the anti-inflammatory effects of caffeine in the muscle can be mediated by modifications on the epigenetic landscape.