Muscle-derived interleukin-6: lipolytic, anti-inflammatory and immune regulatory effects.
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
Pedersen
Bente Klarlund
BK
Dept. of Infectious Diseases, Rigshospitalet, Section 7641, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. bkp@rh.dk
Steensberg
Adam
A
Keller
Pernille
P
Keller
Charlotte
C
Fischer
Christian
C
Hiscock
Natalie
N
van Hall
Gerrit
G
Plomgaard
Peter
P
Febbraio
Mark A
MA
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
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D006003:Glycogen; D005947:Glucose