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Muscle-derived interleukin-6: lipolytic, anti-inflammatory and immune regulatory effects

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Abstract

Interleukin-6 (IL-6) is produced locally in working skeletal muscle and can account for the exercise-induced increase in plasma IL-6. The transcription rate for IL-6 in muscle nuclei isolated from muscle biopsies during exercise is very high and is enhanced further when muscle glycogen content is low. Furthermore, cultured human primary muscle cells can increase IL-6 mRNA when incubated with the calcium ionophore ionomycin and it is likely that myocytes produce IL-6 in response to muscle contraction. The biological roles of muscle-derived IL-6 have been investigated in studies in which human recombinant IL-6 was infused in healthy volunteers to mimic closely the IL-6 concentrations observed during prolonged exercise. Using stable isotopes, we have demonstrated that physiological concentrations of IL-6 induce lipolysis. Although we have yet to determine the precise biological action of muscle-derived IL-6, our data support the hypothesis that the role of IL-6 released from contracting muscle during exercise is to act in a hormone-like manner to mobilize extracellular substrates and/or augment substrate delivery during exercise. In addition, IL-6 inhibits low-level TNF-α production, and IL-6 produced during exercise probably inhibits TNF-α-induced insulin resistance in peripheral tissues. Hence, IL-6 produced by skeletal muscle during contraction may play an important role in the beneficial health effects of exercise

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Acknowledgements

The work from our research laboratories on IL-6 has been supported by The Danish National Research Foundation (#504-14) and The Danish Medical Research Council (22-01-0019).

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  1. Dept. of Infectious Diseases, Rigshospitalet, Section 7641, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Bente Klarlund Pedersen, Adam Steensberg, Pernille Keller, Charlotte Keller, Christian Fischer, Natalie Hiscock & Peter Plomgaard

  2. The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Pernille Keller, Charlotte Keller, Christian Fischer, Natalie Hiscock, Gerrit van Hall & Mark A. Febbraio

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  1. Bente Klarlund Pedersen
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Correspondence to Bente Klarlund Pedersen.

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Pedersen, B.K., Steensberg, A., Keller, P. et al. Muscle-derived interleukin-6: lipolytic, anti-inflammatory and immune regulatory effects. Pflugers Arch - Eur J Physiol 446, 9–16 (2003). https://doi.org/10.1007/s00424-002-0981-z

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