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

Bente Klarlund Pedersen, Adam Steensberg, Pernille Keller, Charlotte Keller, Christian Fischer, Natalie Hiscock, Gerrit van Hall, Peter Plomgaard, Mark A Febbraio


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-alpha production, and IL-6 produced during exercise probably inhibits TNF-alpha-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

Original languageEnglish
JournalPfluegers Archiv
Issue number1
Pages (from-to)9-16
Number of pages8
Publication statusPublished - Apr 2003
Externally publishedYes


  • Animals
  • Anti-Inflammatory Agents
  • Exercise/physiology
  • Glucose/metabolism
  • Glycogen/metabolism
  • Humans
  • Insulin Resistance
  • Interleukin-6/biosynthesis
  • Lipolysis/physiology
  • Muscle Contraction/physiology
  • Muscle, Skeletal/immunology
  • Signal Transduction
  • Tumor Necrosis Factor-alpha/antagonists & inhibitors


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