Interleukin‐6 myokine signaling in skeletal muscle: a double‐edged sword?

Interleukin (IL)‐6 is a cytokine with pleiotropic functions in different tissues and organs. Skeletal muscle produces and releases significant levels of IL‐6 after prolonged exercise and is therefore considered as a myokine. Muscle is also an important target of the cytokine. IL‐6 signaling has been associated with stimulation of hypertrophic muscle growth and myogenesis through regulation of the proliferative capacity of muscle stem cells. Additional beneficial effects of IL‐6 include regulation of energy metabolism, which is related to the capacity of actively contracting muscle to synthesize and release IL‐6. Paradoxically, deleterious actions for IL‐6 have also been proposed, such as promotion of atrophy and muscle wasting. We review the current evidence for these apparently contradictory effects, the mechanisms involved and discuss their possible biological implications. IL‐6 is a cytokine with pleiotropic functions. Skeletal muscle produces and releases IL‐6 after prolonged exercise and is considered a myokine. IL‐6 signaling stimulates hypertrophic muscle growth and de novo myogenesis. However, IL‐6 also promotes atrophy and muscle wasting. We review the current evidence for these apparently contradictory effects, the mechanisms involved and discuss their possible biological implications.