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

1 Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, and 2 Clinical Pathology and Cytology, Center for Laboratory Medicine, University Hospital, Linköping, Sweden Submitted 18 July 2006 ; accepted in final form 30 August 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 E 2 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 wild-type 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. inflammation; food intake; body weight; cytokine; prostaglandin E 2 Address for reprint requests and other correspondence: A. Blomqvist, Division of Cell Biology, Dept. of Biomedicine and Surgery, Faculty of Health Sciences, Linköping Univ., S-581 85, Linköping, Sweden (E-mail: andbl{at}ibk.liu.se )