Antagonism of central glucagon-like peptide-1 receptors enhances lipopolysaccharide-induced fever

Lipopolysaccharide (LPS; a model of systemic bacterial infection) causes fever and activates glucagon-like peptide-1 (GLP-1) neurons in the caudal brainstem. The present study examined whether central GLP-1 receptor signaling plays a functional role in LPS-induced fever. Adult male Sprague-Dawley rats were injected i.p. with LPS (0 or 100 mug/kg), then were infused intracerebroventricularly with GLP-1 receptor antagonist (0 or 10 mug) delivered 2.5 h after injection of LPS or vehicle. Core body temperature was measured at 30-min intervals for 6.5 h after LPS treatment. Consistent with previous reports, body temperature was significantly elevated within 90 min and remained elevated for the remainder of the monitoring period. The pyrogenic effect of LPS was amplified in rats that received central infusion of GLP-1 receptor antagonist, although the antagonist by itself did not alter body temperature. These findings suggest that endogenous GLP-1 acts at central receptors to limit the fever response in rats after i.p. administration of LPS. (C) 2000 Elsevier Science B.V. All rights reserved.