HIGH-DOSE FENTANYL DOES NOT SUPPRESS INTERLEUKIN-1-BETA-INDUCED INCREASES IN PLASMA ACTH AND CORTICOSTERONE IN RATS

Background. High-dose fentanyl anesthesia is reported to attenuate the metabolic and endocrinal responses to surgery. Interleukin-1 (IL-1) i s one of the key mediators in the immunoneuroendocrine system, and may be involved in the stress responses to surgery. We studied whether hi gh-dose fentanyl may influence the IL-lp-induced alterations in plasma ACTH and corticosterone in rats. Methods. Plasma ACTH, corticosterone , blood pressure, heart rate and acid-base status were determined in e ither awake or fentanyl-anesthetized animals immediately before and af ter either phosphate buffered saline or IL-1 beta administration. Fent anyl anesthesia was induced by bolus intravenous injections of fentany l at 50 mu g/kg and pancuronium bromide at 0.2 mg/kg, and maintained b y continuous administrations of fentanyl at 100 or 200 mu g.kg(-1).h(- 1) and pancuronium bromide at 0.4 mu g.kg(-1).h(-1). Results. In awake rats, IL-1 beta at incremental doses of 0.25, 0.5 and 1 mu g/kg incre ased plasma ACTH in a dose-dependent manner, but heat-inactivated IL-1 beta at 4 mu g/kg did not influence plasma ACTH. A noxious stimulus w ith tail clamping for 30 min did not significantly alter plasma ACTH i n fentanyl-anesthetized rats. Fentanyl reduced the basal plasma cortic osterone, but it did not modulate the increases in plasma ACTH and cor ticosterone after the administration of IL-1 beta at 1 mu g/kg. Fentan yl moderately increased the basal blood pressure and heart rate, but i t moderately attenuated the IL-1 beta-induced elevations of blood pres sure and heart rate. IL-1 beta moderately decreased Pco(2) in awake an imals. Conclusions. Fentanyl anesthesia, which is able to suppress the endocrine responses to noxious stimuli, does not attenuate the IL-1 b eta-mediated activation of the pituitary-adrenal axis in rats.