title: Effects of vagotomy on lipopolysaccharide-induced brain interleukin-1beta protein in rats.
abstract: The production of interleukin-1beta (IL-1beta) in brain is thought to be a critical step in the induction of central manifestations of the acute phase response, and the vagus nerve has been implicated in immune-to-brain communication. Thus, this study examined the effects of intraperitoneal (i.p.) injections of lipopolysaccharide (LPS) on brain IL-1beta protein levels in control and subdiaphragmatically vagotomized rats. In the first experiment, vagotomized and sham-operated male Sprague-Dawley rats were injected i.p. with one of three doses (10, 50, 100 microg/kg) of LPS or vehicle (sterile, pyrogen-free saline) and sacrificed 2 h after the injection. In the second experiment, vagotomized and sham-operated rats were injected i.p. with 100 microg/kg LPS or vehicle and sacrificed 1 h after the injection. The i.p. injection of LPS dose-dependently increased IL-1beta protein levels in the hypothalamus, hippocampus, dorsal vagal complex, cerebellum, posterior cortex, and pituitary 2 h after the injection. Brain and pituitary IL-1beta levels were also significantly increased 1 h after the injection of 100 microg/kg LPS. There were no significant differences in brain IL-1beta levels between sham-operated and vagotomized rats at either the 2 h or 1 h time points. The current data are consistent with previous studies showing increases in brain IL-1beta after peripheral injections of LPS, and support the notion that brain IL-1beta is a mediator in the illness-induction pathway. Furthermore, these data indicate that, at the doses and times tested, subdiaphragmatic vagal afferents are not crucial for LPS-induced brain IL-1beta protein.
authors.affiliation: Department of Psychology, University of Colorado at Boulder, 80309-0345, USA. mhansen@psych.colorado.edu
authors.forename: M K
authors.initials: MK
authors.lastname: Hansen
authors.forename: K T
authors.initials: KT
authors.lastname: Nguyen
authors.forename: L E
authors.initials: LE
authors.lastname: Goehler
authors.forename: R P
authors.initials: RP
authors.lastname: Gaykema
authors.forename: M
authors.initials: M
authors.lastname: Fleshner
authors.forename: S F
authors.initials: SF
authors.lastname: Maier
authors.forename: L R
authors.initials: LR
authors.lastname: Watkins
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000276:immunology*; D002531:Cerebellum / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002766:Cholecystokinin / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D015213:Neuroimmunomodulation / Q000502:physiology; D010902:Pituitary Gland / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy; D014630:Vagus Nerve / Q000166:cytology / Q000276:immunology* / Q000601:surgery
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D002766:Cholecystokinin