The Impact of a Polyphenol Treatment on TNF-α-Induced Cytokine Release from C2C12 Myotubes.

Tumour necrosis factor –alpha (TNF‐α) promotes skeletal muscle dysfunction and the effects of systemic increases in cytokines can be exacerbated by further local production of pro‐inflammatory cytokines. Increased levels of dietary polyphenols including resveratrol, Epigallocatechin gallate (EGCG) and curcumin are associated with a reduction in systemic inflammation and may therefore alleviate symptoms of muscle dysfunction. We hypothesised that treatment of C2C12 myotubes with TNF‐α would result in increased production of cytokines by muscle and that prior treatment of myotubes with physiological levels of dietary polyphenols would protect against this. C2C12 myotubes were pre‐treated with 1µM or 10 µM of resveratrol, EGCG or curcumin for 24 hours followed by 5ng/ml or 25ng/ml TNF‐α for 24 hours, with appropriate controls. Release of pro‐inflammatory cytokines IL‐6, MCP‐1/CCL2, RANTES/CCL5 and Keratinocyte Chemoattractant (KC) from C2C12 muscle cells was significantly increased in response to 5 and 25ng/ml TNF‐α (p<0.05) compared with untreated cells. Pre‐treatment with 1µM resveratrol significantly reduced the TNF‐α‐induced release of IL‐6, MCP‐1, RANTES/CCL5 and KC from C2C12 cells (p<0.5). These data suggest that resveratrol may be a potent anti‐inflammatory treatment to reduce the local effects of increased systemic TNF‐α in muscle. Funded by BBSRC and the ME Association.