SUBDIAPHRAGMATIC VAGOTOMY INHIBITS INTRAABDOMINAL 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 acute ly stimulates adrenocorticotropin (ACTH) secretion are not clear. Rece ntly, the vagus has been implicated in mediating peripheral cytokine s ignalling of the brain. To investigate a possible central mechanism fo r peripheral cytokine stimulation of the HPA axis, we tested the hypot hesis 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 (2 0 mu g/kg) IL-1 beta. Vagotomy markedly attenuated plasma ACTH secreti on at 2 h after high-dose IL-1 beta stimulation and abolished plasma A CTH secretion at 2 h after low-dose IL-1 beta stimulation. At 1 h afte r low-dose IL-1 beta, stimulation of plasma ACTH in vagotomized animal s was also markedly diminished compared to sham animals. However, vago tomy did not alter stimulation of plasma corticosterone at 1 or 2 h af ter low-dose IL-1 beta or at 2 h after high-dose IL-1 beta. In additio n, 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 intr a-abdominal (i.p.) IL-1 beta; (2) stimulation of corticosterone secret ion by i.p. IL-1 beta is not altered by vagotomy; and (3) the inhibito ry effect of vagotomy on activation of the HPA axis appears to be spec ific for immune stimulation by cytokines.