STIMULATORY EFFECT OF INTERLEUKIN-1-BETA ON THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS OF THE RAT - INFLUENCE OF AGE, GENDER AND CIRCULATING SEX STEROIDS

The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic-pituitary-adrenal (HPA) axis to the stimulatory influence of interleukins (ILs). It is thus reasonable to assume that inappropriate responses of the HPA axis to ILs might play a role in modulating the onset of pathological conditions such as infections. As part of our programme aimed at investigating the ability of ILs to release proopiomelanocortin-like peptides and corticosterone in rats exposed to alcohol, we observed that this stimulatory action appeared to be influenced by the gender of the animals. We therefore examined the ability of IL-1 beta, injected peripherally, to stimulate the HPA axis as a function of stage of sexual maturation and the presence or absence of circulating sex steroids. In immature (21 to 22-day-old) rats, both males and females responded to the i.p. administration of 0.5 or 2.0 mu g IL-1 beta/kg with statistically comparable increases in plasma ACTH levels. In contrast, females released significantly (P<0.01) more corticosterone in response to the lower dose of cytokine. Forty-day-old intact animals showed no sexual dimorphism in ACTH secretion, but the females again secreted significantly (P<0.05-0.01) more corticosterone. Gonadectomy, performed 7-8 days prior to the assay, increased the absolute amount of corticosterone released over a 60-min period. A noticeable dimorphism of the ACTH response to IL-1 beta became apparent in 70-day-old intact rats, with females secreting more ACTH than males. These females also released significantly more corticosterone than males under both resting and stimulated circumstances. In this age group, gonadectomy abolished the sex difference in terms of ACTH release, but augmented the total amount of corticosteroids secreted by both sexes, as well as increasing the sexual dimorphism. These results suggest the presence of gender differences in the response of the HPA axis to IL-1 beta. While the sexual dimorphism of ACTH secretion appears to be dependent on circulating sex steroids, the sexually dimorphic adrenal response was retained following gonadectomy.