Interleukin-6 in acute exercise and training: what is the biological relevance?

TLDR

Skeletal muscle contraction releases IL‑6 into the interstitium and bloodstream during exercise, and this muscle‑derived IL‑6 dominates the circulating IL‑6 response. Muscle contraction induces IL‑6 synthesis through calcium, glucose, and ROS‑mediated transcriptional activation, and IL‑6 then modulates liver, adipose, HPA axis, and immune cells to shape metabolic and immunological responses. The IL‑6 response magnitude depends on exercise intensity and duration, with mode having little effect; prolonged, large‑muscle activity is required for a marked systemic IL‑6 rise, while training reduces both basal IL‑6 and the acute response, leading to lower resting and exercise‑induced IL‑6 levels.

Abstract

It is now recognized that contracting skeletal muscle may synthesize and release interleukin-6 (IL-6) into the interstitium as well as into the systemic circulation in response to a bout of exercise. Although several sources of IL-6 have been demonstrated, contracting muscles contributes to most of the IL-6 present in the circulation in response to exercise. The magnitude of the exercise-induced IL-6 response is dependent on intensity and especially duration of the exercise, while the mode of exercise has little effect. Several mechanisms may link muscle contractions to IL-6 synthesis: Changes in calcium homeostasis, impaired glucose availability, and increased formation of reactive oxygen species (ROS) are all capable of activating transcription factors known to regulate IL-6 synthesis. Via its effects on liver, adipose tissue, hypothalamic-pituitary-adrenal (HPA) axis and leukocytes, IL-6 may modulate the immunological and metabolic response to exercise. However, prolonged exercise involving a significant muscle mass in the contractile activity is necessary in order to produce a marked systemic IL-6 response. Furthermore, exercise training may reduce basal IL-6 production as well as the magnitude of the acute exercise IL-6 response by counteracting several potential stimuli of IL-6. Accordingly, a decreased plasma IL-6 concentration at rest as well as in response to exercise appears to characterize normal training adaptation.