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1
* The Copenhagen Muscle Research Centre and
The Department of Infectious Diseases, Rigshospitalet, The University of Copenhagen, Copenhagen, Denmark; and
The Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
1Correspondence: Copenhagen Muscle Research Centre, Rigshospitalet, 7652, Tagensvej 20, DK-2200, Copenhagen N, Denmark. E-mail: bkp{at}rh.dk
It has recently been demonstrated that the marked increase in the systemic concentration of cytokine interleukin-6 (IL-6) seen with exercise originates from the contracting limb and that skeletal muscle cells per se are the likely source of the production. This review summarizes the possible mechanisms for activation and biological consequences of muscle-derived IL-6. It appears that intramuscular IL-6 is stimulated by complex signaling cascades initiated by both calcium (Ca2+) -dependent and -independent stimuli. It also seems likely that skeletal muscle produces IL-6 to aid in maintaining metabolic homeostasis during periods of altered metabolic demand such as muscular exercise or insulin stimulation. It may do so via local and/or systemic effects. This review also explores the efficacy that IL-6 may be used as a therapeutic drug in treating metabolic disorders such as obesity, type 2 diabetes, and atherosclerosis.—Febbraio, M. A., Pedersen, B. K. Muscle-derived interleukin 6: mechanisms for activation and possible biological roles.
Key Words: cytokines • lipolysis • intracellular signaling • metabolism • calcium • glycogen • metabolic syndrome
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