title: Subdiaphragmatic vagotomy inhibits intra-abdominal interleukin-1 beta stimulation of adrenocorticotropin secretion.
abstract: Although interleukin (IL)-1 beta activates the hypothalamic-pituitary-adrenal (HPA) axis, the mechanisms by which peripheral IL-1 beta acutely stimulates adrenocorticotropin (ACTH) secretion are not clear. Recently, the vagus has been implicated in mediating peripheral cytokine signalling of the brain. To investigate a possible central mechanism for peripheral cytokine stimulation of the HPA axis, we tested the hypothesis that the vagus mediates IL-1 beta activation of the HPA axis by an intra-abdominal stimulus. We studied the effect of subdiaphragmatic vagotomy on plasma ACTH stimulation in rats by intraperitoneal (i.p.) IL-1 beta. Adult male Sprague-Dawley rats underwent subdiaphragmatic vagotomy or sham surgery 1 week prior to study. Rats were killed 1 and 2 h after i.p. saline (control) and low- (4 micrograms/kg) and high-dose (20 micrograms/kg) IL-1 beta. Vagotomy markedly attenuated plasma ACTH secretion at 2 h after high-dose IL-1 beta stimulation and abolished plasma ACTH secretion at 2 h after low-dose IL-1 beta stimulation. At 1 h after low-dose IL-1 beta, stimulation of plasma ACTH in vagotomized animals was also markedly diminished compared to sham animals. However, vagotomy did not alter stimulation of plasma corticosterone at 1 or 2 h after low-dose IL-1 beta or at 2 h after high-dose IL-1 beta. In addition, vagotomy did not alter stimulation of plasma ACTH or corticosterone secretion by insulin-induced hypoglycemia. We conclude that: (1) the vagus plays an important role in stimulation of ACTH secretion by intra-abdominal (i.p.) IL-1 beta; (2) stimulation of corticosterone secretion by i.p. IL-1 beta is not altered by vagotomy; and (3) the inhibitory effect of vagotomy on activation of the HPA axis appears to be specific for immune stimulation by cytokines.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA. lkapcala@umabnet.ab.umd.edu
authors.forename: L P
authors.initials: LP
authors.lastname: Kapcala
authors.forename: J R
authors.initials: JR
authors.lastname: He
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.forename: J O
authors.initials: JO
authors.lastname: Pieper
authors.forename: L J
authors.initials: LJ
authors.lastname: DeTolla
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone