Interleukin-6 release from human skeletal muscle during exercise: relation to AMPK activity.
Level 2 - randomized trial
Randomized crossover physiological trial in humans
PubMed 12937023 · doi:10.1152/japplphysiol.00242.2003
What was done
Eight healthy, well-trained young men completed two 60-minute cycling trials at 70% peak oxygen uptake under two conditions: glycogen-depleted and glycogen-loaded. Leg IL-6 release, systemic plasma IL-6, and muscle alpha1- and alpha2-AMPK activity were measured at rest and during exercise.
What was found
In the glycogen-depleted state, IL-6 was released from the leg after 10 minutes of exercise, whereas no significant release occurred in the glycogen-loaded state. Systemic plasma IL-6 rose similarly in both states from ~0.8 pg/ml at rest to ~4.5 pg/ml after 60 minutes of exercise. Resting activity of alpha1-AMPK (160%) and alpha2-AMPK (145%) was elevated in glycogen-depleted muscle. Exercise increased alpha2-AMPK activity only in the glycogen-depleted state, while alpha1-AMPK activity was unchanged in both trials. At 60 minutes of glycogen-depleted exercise, individual alpha2-AMPK activity correlated significantly with individual leg IL-6 release (r = 0.87, P < 0.006) and average 60-minute IL-6 release (r = 0.86, P < 0.006).
Why it matters
The study shows that low muscle glycogen accelerates muscle IL-6 release and activates alpha2-AMPK during exercise, indicating that AMPK and IL-6 may interact or act as co-regulated metabolic sensors.
Limits
The sample size is very small (n = 8) and limited exclusively to young, well-trained men. Correlational observations cannot establish causation between AMPK activation and IL-6 release, and non-leg sources of circulating IL-6 were not identified.
Cited by
- contradicts IL-6 is secreted by muscles after exercise rather than during the bout of exercise itself.
- supports The post-exercise spike in IL-6 is particularly pronounced when skeletal muscle glycogen stores are depleted.