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

Abstract

1. Plasma interleukin (IL)-6 concentration is increased with exercise and it has been demonstrated that contracting muscles can produce IL-The question addressed in the present study was whether the IL-6 production by contracting 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 (Wmax). Arterial-femoral venous (a-fv) differences over the exercising and the resting leg were obtained before and every hour during the exercise. Leg blood flow was measured in parallel by the ultrasound Doppler technique. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA). 3. Arterial plasma concentrations for IL-6 increased 19-fold compared to rest. The a-fv difference for IL-6 over the exercising leg followed the same pattern as did the net IL-6 release. Over the resting leg, there was no significant 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 17-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 the plasma. This indicates a very high turnover of IL-6 during muscular exercise. We suggest that IL-6 produced by skeletal contracting muscle contributes to the maintenance of glucose homeostasis during prolonged exercise.

Figure 1. Plasma IL-6 data for 6 male subjects measured before and every hour during 5 h of one-legged concentric exercise

Data are presented as medians and quartiles. A, average of arterial IL-6 plasma concentration. B, average of arterial-femoral venous (a-fv) differences for exercising and resting leg, measured as venous plasma IL-6 concentration minus arterial plasma IL-6 concentration. Note that only increases in the exercising leg are significant. C, net release of IL-6 from exercising and resting leg (Ficks principle: blood flow w a-fv differences). As with the a-fv IL-6 differences, only the increase in the exercising leg is significant and there is a significant difference between the exercising and resting leg at 4 and 5 h. *Significant difference from pre-exercise value (P < 0.05); [dagger]significant difference between exercising and resting leg (P < 0.05).

Figure 2. Blood flow in the exercising and resting leg measured by ultrasound Doppler

Data are means +s.e.m.*Significant difference from pre-exercise (Rest) value (P < 0.05).