Central interleukin-1 partially mediates endotoxin-induced changes in glucose metabolism.
The purpose of the present study was to determine whether intracerebral interleukin (IL)-1 mediates the endotoxin [lipopolysaccharide (LPS)]-induced increase in glucose flux. To accomplish this goal, a specific receptor antagonist for IL-1 (IL-1ra) or artificial cerebrospinal fluid was infused into the lateral ventricle via an intracerebroventricular cannula before, and for 4 h after, the intravenous injection of LPS. Whole body glucose flux was measured in conscious unrestrained rats using [3-3H]glucose. LPS increased both the plasma glucose concentration and the rate of glucose production (95 and 80%, respectively). In contrast, intracerebroventricular infusion of IL-1ra (2 mg/kg + 2 mg-kg-1.h-1) attenuated by approximately 50% the LPS-induced changes in glucose metabolism. IL-1ra also blunted the increase in plasma catecholamines, but not the elevation in glucagon and corticosterone concentrations, observed after LPS. Intracerebroventricular infusion of IL-1ra greatly reduced the LPS-induced hyperlactacidemia but did not alter the increase in muscle pyruvate dehydrogenase activity. An intravenous infusion of a 10-fold greater dose of IL-1ra, however, did not antagonize the LPS-induced increase in glucose flux. These data indicate that a major portion of the stimulation of glucose flux, as well as the increase in plasma catecholamines in response to LPS, is mediated by IL-1 within the central nervous system.
Lang
C H
CH
Department of Surgery, State University of New York at Stony Brook 11794-8191, USA. LANG@SURG.SOM.SUNYSB.EDU
Cooney
R
R
Vary
T C
TC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism; D006728:Hormones / Q000097:blood; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D009994:Osmolar Concentration; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D004731:Endotoxins; D006728:Hormones; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011768:Pyruvate Dehydrogenase Complex; D006003:Glycogen