Regulation of peptide-chain initiation in muscle during sepsis by
interleukin-1 receptor antagonist.
Vary, Thomas C., Laure Voisin,and Robert N. Cooney.
Department of Cellular and Molecular Physiology and Department of
Surgery, Pennsylvania State University, College of Medicine, Hershey,
PA 17033 and 1Laboratoire d'Etude du M[circumflex]etabolisme
Azot[acute]e, INRA Clermont-Theix, 63122 Ceyrat, France
APStracts 3:0098E, 1996.
The mechanism by which interleukin-1 (IL-1) regulates protein
synthesis in skeletal muscle during hypermetabolic sepsis in rats was
investigated. Treatment of septic rats with a specific interleukin-1
receptor antagonist (IL-1ra) prevented the sepsis-induced inhibition
of protein synthesis and translational efficiency in gastrocnemius.
Analysis of ribosomal subunits revealed that the increase in free 40S
and 60S ribosomal subunits observed in septic rats was prevented by
infusion of IL-1ra, indicating peptide-chain initiation was
maintained at control values. The failure of sepsis to inhibit
peptide-chain initiation following infusion of IL-1ra correlated with
a maintenance the -subunit of eukaryotic initiation factor eIF-2B
(eIF-2B ) protein at control values. The alterations in the eIF-2B
protein content in gastrocnemius of septic rats treated with or
without IL-1ra were associated with corresponding changes in the
abundance of eIF-2B mRNA. The results provide evidence that infusion
of IL-1ra attenuates the sepsis-induced inhibition of protein
synthesis by preventing the inhibition of peptide-chain initiation
and downregulation of eIF-2B expression during sepsis.
Received 26 January 1996; accepted in final form 10 April 1996.
APS Manuscript Number E51-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 May 96