INTERLEUKIN-1-BETA ENHANCES CORTICOSTERONE SECRETION BY ACTING DIRECTLY ON THE RAT ADRENAL-GLAND

Interleukin-1 (IL-1), a monokine released by activated monocytes during the acute phase of the inflammatory responses, has been reported to enhance hypophyseal ACTH release mainly by stimulating hypothalamic CRF secretion. We investigated a possible direct effect of IL-1-beta on the adrenal gland of the rat. IL-1-beta was found to dose-lependently (4-8-mu-g/kg) raise corticosterone (B) blood concentration in hypophysectomized rats, without inducing any significant increase in the level of circulating ACTH. IL-1-beta did not affect B production by either isolated rat inner adrenocortical cells or fragments of adrenocortical autotransplants lacking chromaffin cells, but dose-dependently (10(-8)-10(-6) M) enhanced that by adrenal slices including both cortex and medulla. The secretory effect of IL-1-beta (10(-6) M) was completely blocked by both alpha-helical-CRF (10(-6) M) and corticotropin-inhibiting peptide (10(-6) M), two competitive inhibitors which (at these concentrations) were able to annul B response of adrenal slices to CRF (10(-6) M) and ACTH (10(-8) M), respectively. In light of many findings indicating that adrenal medulla contains and releases CRF and numerous POMC-derived peptides (including ACTH), the hypothesis is advanced that the mechanism underlying the direct secretory effect of IL-1-beta on the adrenal gland may involve the activation of an intraadrenal CRF/ACTH system.