This review examines how exercise produces anti-inflammatory effects through signaling molecules released by contracting muscle. During exercise, skeletal muscle releases large amounts of interleukin-6 (IL-6), which acts as a signaling molecule rather than a marker of inflammation. This temporary rise in IL-6 suppresses production of the pro-inflammatory cytokine tumor necrosis factor (TNF) while also stimulating fat oxidation and supporting glucose regulation.

This response is very different from the inflammatory cascade seen in infection or metabolic disease, where TNF rises first and drives systemic inflammation. The authors propose that repeated bouts of exercise produce an overall anti-inflammatory state, partly by reducing visceral fat and partly through these muscle-derived signaling molecules—often called myokines. These mechanisms may help explain why regular physical activity is strongly associated with lower risk of metabolic syndrome, type 2 diabetes, and cardiovascular disease.

https://journals.physiology.org/doi/full/10.1152/japplphysiol.00164.2004