EVIDENCE THAT INTERLEUKIN-6 IS PRODUCED IN HUMAN SKELETAL-MUSCLE DURING PROLONGED RUNNING

1. This study was performed to test the hypothesis that inflammatory c ytokines are produced in skeletal muscle in response to prolonged inte nse exercise. Muscle biopsies and blood samples were collected from ru nners before, immediately after, and 2 h after a marathon race. 2. 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 t o 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-exer cise. 3. The comparative polymerase chain reaction technique was used to evaluate mRNA for IL-6, IL-1ra, IL-1 beta and tumour necrosis facto r (TNF)-alpha in skeletal muscle and blood mononuclear cells (BMNC) (n =8). Before exercise, mRNA for IL-6 could not be detected either in mu scle 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 -1 beta mRNA were found in one muscle and four BMNC samples after exer cise. TNF-alpha mRNA was not detected in any samples. 4. This study su ggests that exercise-induced destruction of muscle fibres in skeletal muscles may trigger local production of IL-6, which stimulates the pro duction of IL-1ra from circulating BMNC.