title: Muscle-derived interleukin-6: lipolytic, anti-inflammatory and immune regulatory effects.
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-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
authors.affiliation: Dept. of Infectious Diseases, Rigshospitalet, Section 7641, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. bkp@rh.dk
authors.forename: Bente Klarlund
authors.initials: BK
authors.lastname: Pedersen
authors.forename: Adam
authors.initials: A
authors.lastname: Steensberg
authors.forename: Pernille
authors.initials: P
authors.lastname: Keller
authors.forename: Charlotte
authors.initials: C
authors.lastname: Keller
authors.forename: Christian
authors.initials: C
authors.lastname: Fischer
authors.forename: Natalie
authors.initials: N
authors.lastname: Hiscock
authors.forename: Gerrit
authors.initials: G
authors.lastname: van Hall
authors.forename: Peter
authors.initials: P
authors.lastname: Plomgaard
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D015444:Exercise / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008066:Lipolysis / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D006003:Glycogen; D005947:Glucose