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1 Human Physiology, Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
2 Rigshospitalet, Copenhagen Muscle Research Centre,, Copenhagen, Denmark
* To whom correspondence should be addressed. E-mail: erichter{at}aki.ku.dk.
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 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 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 about 0.8 pg ml-1 at rest to about 4.5 pg ml-1 after 60 min exercise. Activity of 
1-(160%), and 2-AMPK (145%) were increased at rest in the glycogen depleted compared with the loaded situation. During exercise 1-AMPK activity did not change from resting levels in both trials whereas 2-AMPK activity increased only in the glycogen depleted state. After 60 min of exercise in the glycogen depleted state individual values of 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.
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