Central interleukin-1 partially mediates endotoxin-induced changes
in glucose metabolism.
Lang, Charles H., 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 Cellular & Molecular Physiology, and the Department
of Surgery, Pennsylvania State University, College of Medicine,
Hershey, PA 17033
APStracts 3:0077E, 1996.
The purpose of the present study was to determine whether
intracerebral interleukin (IL)-1 mediates the endotoxin (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 (ICV) cannula prior to, and for 4 h after,
the intravenous (IV) 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, ICV
infusion of IL-1ra (2 mg/kg + 2 mg/kg/h) attenuated by 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. ICV infusion of
IL-1ra greatly reduced the LPS-induced hyperlactacidemia, but did not
alter the increase in muscle pyruvate dehydrogenase activity. An IV
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.
Received 11 January 1996; accepted in final form 29 March 1996.
APS Manuscript Number E12-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 23 April 96