Interleukin-1 receptor antagonist attenuates sepsis-induced
alterations in the igf system and protein synthesis.
Lang, Charles H., Jie Fan, Robert Cooney, Thomas C. Vary.
Division of Surgical Research, Department of Surgery, State
University of New York at Stony Brook, Stony Brook, NY 11794-8191 and
Department of Surgery, and Department of Cellular and Molecular
Physiology, Pennsylvania State University, College of Medicine,
Hershey, PA 17033
APStracts 2:0239E, 1995.
The purpose of the present investigation was to determine whether
endogenously produced interleukin (IL)-1 mediates the changes in
insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBPs)
induced by chronic abdominal sepsis in rats, and to correlate the
changes in the IGF system with the alterations in protein synthesis.
A constant infusion of IL-1 receptor antagonist (IL-1ra) was begun
after the induction of sepsis and continued for 5 days. Sepsis
decreased IGF-I levels in the blood, liver and gastrocnemius muscle,
increased content in kidney, and did not alter IGF-I levels in heart,
jejunum and spleen. IL-1ra attenuated the sepsis-induced decrease in
plasma IGF-I, and completely prevented the changes in IGF-I observed
in liver, kidney and the gastrocnemius. IGFBP-1 was increased in the
blood, liver and muscle of septic rats. IL-1ra prevented this
increase in IGFBP-1 in blood and liver, but not muscle. The rate of
in vivo protein synthesis was decreased in the gastrocnemius and
kidney, and unaltered in the heart, liver, jejunum and spleen. A
strong linear correlation existed between levels of IGF-I and the
rate of protein synthesis determined simultaneously in the
gastrocnemius. These results provide evidence for the role of IL-1 as
an endogenous mediator of the sepsis-induced changes in IGF-I and
IGFBP-1, and suggest that the accompanying changes in muscle protein
synthesis are partially mediated via changes in IGF-I.
Received 10 August 1995; accepted in final form 4 October 1995.
APS Manuscript Number E380-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95