Subdiaphragmatic vagotomy inhibits intra-abdominal interleukin-1 beta stimulation of adrenocorticotropin secretion

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 mu g/kg) and high-dose (20 mu g/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.