Interleukin‐6 production in contracting human skeletal muscle is influenced by pre‐exercise muscle glycogen content

Abstract

Physical exercise induces a marked elevation in the plasma level of the cytokine interleukin-6 (IL)-6 (Ostrowski et al. 1998a;Pedersen & Hoffman-Goetz, 2000).A novel role has recently been proposed for IL-6 in exercise.The hypothesis being that contracting skeletal muscles produce and release IL-6, which acts in a hormone-like manner possibly mediating a link to the liver, thereby contributing to the substrate homeostasis in prolonged exercise (Steensberg et al. 2000).This hypothesis was supported in a perspective written by Gleeson, 2000.We have found that IL-6 gene expression is increased in both rat (Jonsdottir et al. 2000) and human (Ostrowski et al. 1998b; Starkie et al. 2001a) skeletal muscle following contraction.Although these studies only suggest that muscle is the source of the increase, we have measured the net skeletal muscle IL-6 release from a concentric exercising leg in humans, demonstrating that it could more than account for the exercise-related increase in plasma IL-6 concentrations (Steensberg et al. 2000).Furthermore, Malm et al. 2000 found expression of IL-6 in human muscle cells using immunohistochemistry.Recently, it was demonstrated that circulating monocytes do not contribute to the increase in plasma IL-6 concentrations during exercise (Starkie et al. 2000(Starkie et al. , 2001b)).During prolonged knee-extensor exercise, the IL-6 release was not observed before 2 h (Steensberg et al. 2000).Thereafter, it rose steadily and increased markedly after 4 h.Exercise of this intensity and duration results in muscle glycogen depletion and hypoglycaemia is sometimes also observed (Coggan & Coyle, 1991).It is possible, therefore, that IL-6 production during exercise may be related to an increased dependence on an uptake of blood borne substances by the active muscles.This hypothesis is plausible given the observation that carbohydrate ingestion during prolonged exercise attenuates the plasma IL-6 response (Nehlsen-Cannarella et al. 1997;Nieman et al. 1998), while commencing exercise in a glycogen-depleted state augments the plasma IL-6Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content