IL-1 receptor antagonist attenuates sepsis-induced alterations in the IGF system and protein synthesis.
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 (IGFBP) induced by chronic abdominal sepsis in rats and to correlate the changes in the IGF system with the alternations in protein synthesis. A constant infusion of IL-1 receptor antagonist (IL-1ra) was begun after the induction of sepsis and was continued for 5 days. Sepsis decreased IGF-I levels in the blood, liver, and gastrocnemius muscle, increased the content in the 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 in 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.
Lang
C H
CH
Department of Surgery, State University of New York at Stony Brook, New York 11794-8191, USA.
Fan
J
J
Cooney
R
R
Vary
T C
TC
D000818:Animals; D016470:Bacteremia / Q000378:metabolism*; D001442:Bacteroides Infections / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004927:Escherichia coli Infections / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D007583:Jejunum / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012795:Sialoglycoproteins / Q000494:pharmacology*; D013154:Spleen / Q000378:metabolism
D018970:Insulin-Like Growth Factor Binding Protein 1; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003345:Corticosterone