TY - JOUR
T1 - Muscle-derived interleukin-6: lipolytic, anti-inflammatory and immune regulatory effects.
AU - Pedersen, Bente Klarlund
AU - Steensberg, Adam
AU - Keller, Pernille
AU - Keller, Charlotte
AU - Fischer, Christian
AU - Hiscock, Natalie
AU - van Hall, Gerrit
AU - Plomgaard, Peter
AU - Febbraio, Mark A
N1 - Keywords: Animals; Anti-Inflammatory Agents; Exercise; Glucose; Glycogen; Humans; Insulin Resistance; Interleukin-6; Lipolysis; Muscle Contraction; Muscle, Skeletal; Signal Transduction; Tumor Necrosis Factor-alpha
PY - 2003
Y1 - 2003
N2 - 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
AB - 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
U2 - 10.1007/s00424-002-0981-z
DO - 10.1007/s00424-002-0981-z
M3 - Journal article
C2 - 12690457
SN - 0031-6768
VL - 446
SP - 9
EP - 16
JO - Pflügers Archiv - European Journal of Physiology
JF - Pflügers Archiv - European Journal of Physiology
IS - 1
ER -