IL-1 and LPS induce anorexia by distinct mechanisms differentially dependent on microsomal prostaglandin E synthase-1

Elander L, Engström L, Hallbeck M, Blomqvist A. IL-1 and LPS induce anorexia by distinct mechanisms differentially dependent on microsomal prostaglandin E synthase-1. Am J Physiol Regul Integr Comp Physiol 292: R258–R267, 2007. First published August 31, 2006; doi:10.1152/ajpregu.00511.2006.—Recent work demonstrated that the febrile response to peripheral immune stimulation with proinflammatory cytokine IL-1 or bacterial wall lipopolysaccharide (LPS) is mediated by induced synthesis of prostaglandin E2 by the terminal enzyme microsomal prostaglandin E synthase-1 (mPGES-1). The present study examined whether a similar mechanism might also mediate the anorexia induced by these inflammatory agents. Transgenic mice with a deletion of the Ptges gene, which encodes mPGES-1, and wild-type controls were injected intraperitoneally with IL-1 , LPS, or saline. Mice were free fed, and food intake was continuously monitored with an automated system for 12 h. Body weight was recorded every 24 h for 4 days. The IL-1 induced anorexia in wild-type but not knock-out mice, and so it was almost completely dependent on mPGES-1. In contrast, LPS induced anorexia of the same magnitude in both phenotypes, and hence it was independent of mPGES-1. However, when the mice were prestarved for 22 h, LPS induced anorexia and concomitant body weight loss in the knock-out animals that was attenuated compared with the wildtype controls. These data suggest that IL-1 and LPS induce anorexia by distinct immune-to-brain signaling pathways and that the anorexia induced by LPS is mediated by a mechanism different from the fever induced by LPS. However, nutritional state and/or motivational factors also seem to influence the pathways for immune signaling to the brain. Furthermore, both IL-1 and LPS caused reduced meal size but not meal frequency, suggesting that both agents exerted an anhedonic effect during these experimental conditions.