Evidence that interleukin‐6 is produced in human skeletal muscle during prolonged running

Abstract

This study was performed to test the hypothesis that inflammatory cytokines are produced in skeletal muscle in response to prolonged intense exercise. Muscle biopsies and blood samples were collected from runners before, immediately after, and 2 h after a marathon race. The concentration of interleukin (IL)‐6 protein in plasma increased from 1.5 ± 0.7 to 94.4 ± 12.6 pg ml−1 immediately post‐exercise and to 22.1 ± 3.8 pg ml−1 2 h post‐exercise. IL‐1 receptor antagonist (IL‐1ra) protein in plasma increased from 123 ± 23 to 2795 ± 551 pg ml−1, and increased further to 4119 ± 527 pg ml−1 2 h post‐exercise. The comparative polymerase chain reaction technique was used to evaluate mRNA for IL‐6, IL‐1ra, IL‐1β and tumour necrosis factor (TNF)‐α in skeletal muscle and blood mononuclear cells (BMNC) (n= 8). Before exercise, mRNA for IL‐6 could not be detected either in muscle or in BMNC, and was only detectable in muscle biopsies (5 out of 8) after exercise. Increased amounts of mRNA for IL‐1ra were found in two muscle biopsies and five BMNC samples, and increased amounts of IL‐1β mRNA were found in one muscle and four BMNC samples after exercise. TNF‐α mRNA was not detected in any samples. This study suggests that exercise‐induced destruction of muscle fibres in skeletal muscles may trigger local production of IL‐6, which stimulates the production of IL‐1ra from circulating BMNC.

Exercise effects on systemic immunity

“…32,33 Monocytes and neutrophils invade the inflamed area and phagocytose debris. The increase in blood granulocyte and monocyte phagocytosis may therefore represent a part of the inflammatory response to acute muscle injury.…”

Highly Sensitive Determination of Plasma Cytokines by Time-Resolved Fluoroimmunoassay; Effect of Bicycle Exercise on Plasma Level of Interleukin-1 (IL-1), Tumor Necrosis Factor a (TNF a), and Interferon γ (IFN γ)

“…Secondly, after exercise, IL-6 mRNA was detected in biopsied muscle, which was not found before. 19 Thirdly, TNF α levels increased after hard exercises which involve such contractions and expansions of muscles as occur during hill running, and which give more damage to muscle fibers. 18,20 In our study, TNF α increased in heavier exercises, and this supports the general supposition that this cytokine is produced by damaged myocytes.…”

Interleukin-6 regulates pancreatic α-cell mass expansion

“…Plasma IL-6 levels are acutely elevated following muscle contraction and chronically during obesity (8,9). With respect to its actions in regulating whole body metabolism, IL-6 is involved in the central control of obesity, in the regulation of insulin action, and in the mobilization of energy stores during exercise (10,11).…”