title: Inflammation-induced anorexia and fever are elicited by distinct prostaglandin dependent mechanisms, whereas conditioned taste aversion is prostaglandin independent.
abstract: Systemic inflammation evokes an array of brain-mediated responses including fever, anorexia and taste aversion. Both fever and anorexia are prostaglandin dependent but it has been unclear if the cell-type that synthesizes the critical prostaglandins is the same. Here we show that pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not of COX-1, attenuates inflammation-induced anorexia. Mice with deletions of COX-2 selectively in brain endothelial cells displayed attenuated fever, as demonstrated previously, but intact anorexia in response to peripherally injected lipopolysaccharide (10μg/kg). Whereas intracerebroventricular injection of a cyclooxygenase inhibitor markedly reduced anorexia, deletion of COX-2 selectively in neural cells, in myeloid cells or in both brain endothelial and neural cells had no effect on LPS-induced anorexia. In addition, COX-2 in myeloid and neural cells was dispensable for the fever response. Inflammation-induced conditioned taste aversion did not involve prostaglandin signaling at all. These findings collectively show that anorexia, fever and taste aversion are triggered by distinct routes of immune-to-brain signaling.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Nilsson
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Sweden; Department of Emergency Medicine, Linköping University, Linköping, Sweden.
authors.forename: Daniel Björk
authors.initials: DB
authors.lastname: Wilhelms
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Sweden.
authors.forename: Elahe
authors.initials: E
authors.lastname: Mirrasekhian
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Sweden.
authors.forename: Maarit
authors.initials: M
authors.lastname: Jaarola
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Blomqvist
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Sweden. Electronic address: david.engblom@liu.se.
authors.forename: David
authors.initials: D
authors.lastname: Engblom
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors; D005334:Fever / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides; D051379:Mice; D013649:Taste / Q000187:drug effects / Q000502:physiology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2
keywords: Anorexia; Conditioned place aversion; Cyclooxygenase; Fever; Inflammation; Lipopolysaccharide