Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content

In humans, the plasma interleukin 6 (IL-6) concentration increases dramatic ally during low-intensity exercise. Measurements across the working limb in dicate that skeletal muscle is the source of IL-6 production. To determine whether energy availability influences the regulation of IL-6 expression du ring prolonged exercise, six male subjects completed two trials consisting of 180 min of two-legged dynamic knee extensor with either normal or low (s imilar to 60% of control) preexercise muscle glycogen levels. Increases in plasma IL-6 during exercise were significantly higher (P<0.05) in the low-g lycogen (16-fold) trial verses the control (10-fold) trial. Transcriptional activation of the IL-6 gene in skeletal muscle was also higher in the low- glycogen trial; it increased by about 40-fold after 90 min of exercise and about 60-fold after 180 min of exercise. Muscle IL-6 mRNA followed a simila r but delayed pattern, increasing by more than 100-fold in the low-glycogen trial and by about 30-fold in the control trial. These data demonstrate th at exercise activates transcription of the IL-6 gene in working skeletal mu scle, a response that is dramatically enhanced when glycogen levels are low . These findings also support the hypothesis that IL-6 may be produced by c ontracting myofibers when glycogen levels become critically low as a means of signaling the liver to increase glucose production.