Effects of vagotomy on lipopolysaccharide-induced brain interleukin-1beta protein in rats.
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.
Hansen
M K
MK
Department of Psychology, University of Colorado at Boulder, 80309-0345, USA. mhansen@psych.colorado.edu
Nguyen
K T
KT
Goehler
L E
LE
Gaykema
R P
RP
Fleshner
M
M
Maier
S F
SF
Watkins
L R
LR
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
D007375:Interleukin-1; D008070:Lipopolysaccharides; D002766:Cholecystokinin