title: Thermogenic and corticosterone responses to intravenous cytokines (IL-1beta and TNF-alpha) are attenuated by subdiaphragmatic vagotomy.
abstract: The brain orchestrates changes in behavior and physiology as a consequence of peripheral immune activation and infection. These changes require that the brain receives signals from the periphery that an immunological challenge has occurred. Previous research has established that cytokines play a role in signalling the brain. What remains unclear, however, is how peripheral cytokines signal the central nervous system. A recent proposal is that cytokines signal the brain by stimulating peripheral nerves. The hypothesis states that following infection and the release of cytokines such as IL-1beta into local tissue or microvasculature, IL-1beta stimulates IL-1 receptors on vagal afferent terminals, or more likely on cells of vagal paraganglia. Vagal afferents, in turn, signal the brain. Previous work has demonstrated that transection of the vagus below the level of the diaphragm blocks or attenuates many illness consequences of intraperitoneally (i.p.) administered lipopolysaccharide (LPS) or IL-1beta. The present studies extend these findings by examining the effect of subdiaphragmatic vagotomy on illness consequences following intravenously (i.v.) administered IL-1beta and TNF-alpha. Subdiaphragmatic vagotomy attenuated both the fever response and corticosterone response produced by i.v. administered cytokines. This effect was dose dependent. The results add support to the hypothesis that vagal afferents are involved in peripheral cytokine-to-brain communication.
authors.affiliation: Department of Kinesiology and Applied Physiology, University of Colorado at Boulder, 80309-0354, USA. fleshner@spot.colorado.edu
authors.forename: M
authors.initials: M
authors.lastname: Fleshner
authors.forename: L E
authors.initials: LE
authors.lastname: Goehler
authors.forename: B A
authors.initials: BA
authors.lastname: Schwartz
authors.forename: M
authors.initials: M
authors.lastname: McGorry
authors.forename: D
authors.initials: D
authors.lastname: Martin
authors.forename: S F
authors.initials: SF
authors.lastname: Maier
authors.forename: L R
authors.initials: LR
authors.lastname: Watkins
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D003964:Diaphragm / Q000294:innervation; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000276:immunology* / Q000601:surgery
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003345:Corticosterone