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J Appl Physiol 95: 2273-2277, 2003. First published August 22, 2003; doi:10.1152/japplphysiol.00242.2003
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Interleukin-6 release from human skeletal muscle during exercise: relation to AMPK activity

Christopher MacDonald,1 Jørgen F. P. Wojtaszewski,1 Bente Klarlund Pedersen,2 Bente Kiens,1 and Erik A. Richter1

1Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, and 2Department of Infectious Diseases, Rigshospitalet, DK-1200 Copenhagen, Denmark

Submitted 10 March 2003 ; accepted in final form 30 July 2003

We tested the hypothesis that IL-6 release from muscle during exercise may be related to muscle activity of 5'-AMP-activated protein kinase (AMPK). Eight healthy, well-trained young men completed two 60-min trials on a bicycle ergometer at 70% of their peak oxygen uptake in either a glycogen-depleted or a glycogen-loaded state. IL-6 was released from the leg already after 10 min of exercise in the glycogen-depleted state, whereas no significant release was observed at any time in the loaded state. Nevertheless, plasma IL-6 increased similarly in the two trials from ~0.8 pg/ml at rest to ~4.5 pg/ml after 60 min of exercise. Activity of {alpha}1-AMPK (160%) and {alpha}2-AMPK (145%) was increased at rest in the glycogen-depleted compared with the loaded situation. During exercise, {alpha}1-AMPK activity did not change from resting levels in both trials, whereas {alpha}2-AMPK activity increased only in the glycogen-depleted state. After 60 min of exercise in the glycogen-depleted state, individual values of {alpha}2-AMPK activity correlated significantly (r = 0.87, P < 0.006) with individual values of IL-6 release as well as with average IL-6 release over the entire 60 min (r = 0.86, P < 0.006). The present data are compatible with a role for AMPK in IL-6 release during exercise or a role for IL-6 in activating AMPK. Alternatively, both AMPK and IL-6 are independent sensors of a low muscle glycogen concentration during exercise. In addition, leg release of IL-6 cannot alone explain the increase in plasma IL-6 during exercise.

interleukins; glycogen; 5'-AMP-activated protein kinase


Address for reprint requests and other correspondence: E. A. Richter, Copenhagen Muscle Research Centre, Dept. of Human Physiology, Institute of Exercise and Sport Sciences, Univ. of Copenhagen, 13 Universitetsparken, DK-2100 Copenhagen, Denmark (E-mail: erichter{at}aki.ku.dk).




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