Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6

1. Plasma interleukin (IL)-6 concentration is increased with exercise and i t has been demonstrated that contracting muscles can produce IL-6. The ques tion addressed in the present study was whether the IL-6 production by cont racting skeletal muscle is of such a magnitude that it can account for the IL-6 accumulating in the blood. 2. This was studied in six healthy males, who performed one-legged dynamic knee extensor exercise for 5 h at 25 W, which represented 40% of peak power output (W-max). Arterial-femoral venous (a-fv) differences over the exerci sing and the resting leg were obtained before and every hour during the exe rcise. Leg blood flow was measured in parallel by the ultrasound Doppler te chnique. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA). 3. Arterial plasma concentrations for IL-6 increased 19-fold compared to re st. The a-fv difference for IL-6 over the exercising leg followed the same pattern as did the net IL-B release. Over the resting leg, there was no sig nificant a-fv difference or net IL-6 release. The work was produced by 2.5 kg of active muscle, which means that during the last 2 h of exercise, the median IL-6 production was 6.8 ng min(-1) (kg active muscle)(-1) (range, 3. 96-9.69 ng min(-1) kg(-1)). 4. The net IL-6 release from the muscle over the last 2 h of exercise was 1 7-fold higher than the elevation in arterial IL-6 concentration and at 5 h of exercise the net release during 1 min was half of the IL-6 content in th e plasma. This indicates a very high turnover of IL-6 during muscular exerc ise. We suggest that IL-6 produced by skeletal contracting muscle contribut es to the maintenance of glucose homeostasis during prolonged exercise.