RESPONSE OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS TO INTERLEUKIN-1 IN THE AGING RAT

Plasma ACTH levels after intravenous i.v. injection of IL-1alpha (IL-1) were measured in 2- and 24-month-old Sprague-Dawley rats. Blood samples were withdrawn at -30, 0, 30, 60, 90 and 120 min after IL-1 injection. In addition, the effects of IL-1 and serotonin (5-HT) on in vitro CRH secretion and content in hypothalami from 2- and 24-month-old rats were investigated. IL-1 injection stimulated ACTH secretion in a dose-related manner, in both 2- and 24-month-old rats. The peak of the effect occurred 60 min after the injection. ACTH levels returned to baseline within 120 min in 2-month-old rats. Plasma ACTH levels in untreated 24-month-old rats returned to baseline 240 min after injection. In vitro incubation of rat hypothalami with either IL-1 or 5-HT at equimolar concentrations resulted in the stimulation of immunoreactive CRH (iCRH) secretion from both 2- and 24-month-old hypothalami. However, the iCRH content in the latter was increased vs. basal if compared to 2-month-old rats. These results suggest the feedback between IL-1 and the hypothalamic-pituitary-adrenal axis is altered during aging.