Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle

Robert N. Cooney, George O. Maish, Tracie Gilpin, Margaret L. Shumate, Charles H. Lang, Thomas C. Vary

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Chronic interleukin (IL)-1 administration is associated with negative nitrogen balance and the loss of lean body mass. To elucidate the molecular mechanism(s) by which IL-1 modulates protein metabolism in muscle, we investigated the effects of chronic (6 day) IL-1α infusion on protein synthesis in individual muscles (gastrocnemius, soleus, heart) compared with saline-infused control rats. IL-1 significantly decreased muscle weight, protein content, and the rate of protein synthesis in gastrocnemius (fast-twitch muscle). IL-1 had no effect on these parameters in the heart, whereas only the rate of protein synthesis was reduced in soleus (slow-twitch muscle). The reduction in gastrocnemius protein synthesis was not the result of a decrease in total RNA content, but was associated with a diminished translational efficiency. The diminished translational efficiency correlated with a 40% reduction in the ∈-subunit of eukaryotic initiation factor 2B (elF2B∈) in gastrocnemius from IL-1-treated animals. However, the content of the α-subunit of elF2 (elF2α) was unaffected. In contrast, the elF2α content in heart was increased by IL-1, although elF2B∈ levels were unchanged. Reductions in skeletal muscle protein synthesis were not associated with a concomitant reduction in circulating or tissue content of insulin-like growth factor I. In summary, the IL-1-induced decrease in gastrocnemius protein synthesis appears to be regulated at the level of RNA translation via a reduction in elF2B∈. These findings support a regulatory role for IL-1 as a mediator of muscle protein synthesis and the alterations in body composition observed in catabolic states where this cytokine is overexpressed.

Original languageEnglish (US)
Pages (from-to)235-241
Number of pages7
JournalShock
Volume11
Issue number4
DOIs
StatePublished - Apr 1999

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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