Role of central IL-1 in regulating peripheral IGF-I during endotoxemia and sepsis.
Inflammatory cytokines may mediate the host response to infection via central nervous system, endocrine, and/or paracrine/autocrine signaling mechanisms. Previous studies have shown that intravenous administration of interleukin (IL)-1 beta alters the concentration of the anabolic hormone insulin-like growth factor (IGF)-I in plasma and various tissues. The purpose of the present study was to determine 1) whether the intracerebroventricular injection of IL-1 beta can influence peripheral IGF-I levels in control animals and 2) whether the central administration of a IL-1 receptor antagonist (IL-1ra) can prevent the changes in peripheral IGF-I induced by endotoxin [lipopolysaccharide (LPS)] or sepsis produced by cecal ligation and puncture. In the first experiment, injection of IL-1 beta (100 ng/rat) decreased IGF-I levels in plasma, liver, and gastrocnemius muscle 28-36% by 1.5 h in conscious fasted rats. IGF-I levels remained reduced at 3 h, but returned to baseline by 6 h. IGF-I content was not altered in soleus, kidney, spleen, intestine, or whole brain after IL-1 beta. In the second series of experiments, LPS injected intravenously decreased IGF-I levels in plasma, liver, and gastrocnemius at 1.5 h, and levels were even further reduced at 3 and 6 h in these tissues (59, 57, and 48%, respectively). Moreover, the IGF-I content was also decreased in soleus (30-35%) and increased in kidney (2- to 3-fold) after LPS. In the third experiment, changes in IGF-I levels in plasma and tissues, similar to those seen in LPS-treated rats, were detected 24 h after induction of peritonitis. Intracerebroventricular infusion of IL-1ra did not alter any of the changes in IGF-I produced by either LPS or sepsis, although it did attenuate the concomitant changes in growth hormone levels. These data suggest that, although central IL-1 beta is capable of modulating peripheral IGF-I levels, central administration of IL-1ra was unable to modulate the changes in peripheral IGF-I in blood and tissues produced by either endotoxemia or peritonitis.
Lang
C H
CH
Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey 17033, USA. clang@psu.edu
Fan
J
J
Wojnar
M M
MM
Vary
T C
TC
Cooney
R
R
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002432:Cecum; D003345:Corticosterone / Q000097:blood; D019446:Endotoxemia / Q000378:metabolism*; D013006:Growth Hormone / Q000097:blood; D007239:Infections / Q000209:etiology / Q000378:metabolism*; D007276:Injections, Intraventricular; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D008026:Ligation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010538:Peritonitis / Q000097:blood / Q000209:etiology; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors
D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003345:Corticosterone