Prostaglandins and interleukin-1beta in the hypothalamic-pituitary-adrenal response to systemic phenylephrine under...

We investigated the role of interleukin-1beta (IL-1beta) and prostaglandins (PG) in the alpha(1)-adrenergic agonist, phenylephrine-induced hypothalamic-pituitary-adrenal axis (HPA) responses under basal and social stress conditions. Male Wistar rats, either control or exposed to crowding stress for 7 days prior to treatment, were used in these experiments. All compounds were injected i.p. Cyclooxygenase COX-1 and COX-2 inhibitors, piroxicam and compound NS-398, IL-1beta and IL-1beta receptor antagonist (IL-1betaRA) were injected 15 min before phenylephrine. Plasma ACTH and serum corticosterone levels were measured 1 h after phenylephrine or IL-1beta injection. Phenylephrine, in respective higher dose administered systemically (0.4 mg/kg i.p.) was almost equally effective as given i.c.v. (30 microg) in stimulating ACTH and corticosterone secretion. Likewise, the extent of the involvement of PG generated by COX-1 and COX-2 in the phenylephrine-induced ACTH and corticosterone secretion was similar after systemic or i.c.v. treatment under both resting and stress conditions. Piroxicam, stronger than compound NS-398, reduced the i.p. phenylephrine-induced ACTH and corticosterone secretion. IL-1beta receptor antagonist (50 microg/kg i.p.) did not significantly affect the inhibitory action of piroxicam on the i.p. phenylephrine-induced ACTH and corticosterone secretion in control rats, but significantly enhanced the inhibition evoked by piroxicam in stressed rats. IL-1beta (2.5 microg/kg i.p.) significantly increased ACTH and corticosterone secretion under basal conditions. Crowding stress for 7 days markedly impaired the IL-1beta-induced ACTH and corticosterone secretion. The mechanism of the stimulatory action of i.p. IL-1beta, which does not cross the blood-brain barrier, may comprise both central and peripheral components of the HPA axis. These results suggest that under basal conditions IL-1beta is not markedly involved in the alpha(1)-adrenergic agonist-induced stimulation of the HPA axis activity. During social crowding stress IL-1beta and prostaglandins are significantly involved in this stimulation.