Inhibition of muscle insulin-like growth factor I expression by tumor necrosis factor-alpha

Am J Physiol Endocrinol Metab. 2002 Dec;283(6):E1279-90. doi: 10.1152/ajpendo.00054.2002. Epub 2002 Jul 2.


The role of TNF-alpha in muscle catabolism is well established, but little is known about the mechanisms of its catabolic action. One possibility could be that TNF-alpha impairs the production of local growth factors like IGF-I. The aim of this study was to investigate whether TNF-alpha can directly inhibit IGF-I gene and protein expression in muscle. First, we investigated whether the acute inflammation induced by endotoxin injection changes IGF-I and TNF-alpha mRNA in rat tibialis anterior muscle. Endotoxin rapidly increased TNF-alpha mRNA (7-fold at 1 h, P < 0.001) and later decreased IGF-I mRNA (-73% at 12 h, P < 0.001). Furthermore, in a model of C2C12 myotubes, TNF-alpha strongly inhibited IGF-I mRNA and protein (-73 and -47% after 72 h, P < 0.001 and P < 0.01, respectively). Other proinflammatory cytokines failed to inhibit IGF-I mRNA. The effect of TNF-alpha on IGF-I mRNA was not mediated by nitric oxide, and the activation of NF-kappaB was insufficient to inhibit IGF-I expression. Taken together, our data suggest that TNF-alpha induced in muscle after LPS injection can locally inhibit IGF-I expression. The inhibition of muscle IGF-I production could contribute to the catabolic effect of TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Line
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects*
  • In Vitro Techniques
  • Insulin-Like Growth Factor I / biosynthesis*
  • Insulin-Like Growth Factor I / genetics
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-6 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism*
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Tumor Necrosis Factor / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Insulin-Like Growth Factor I
  • Interferon-gamma