INTERLEUKIN-1-INDUCED CORTICOSTERONE RELEASE OCCURS BY AN ADRENERGIC MECHANISM FROM RAT ADRENAL-GLAND

Interleukin-1 (IL-1) has been shown to stimulate corticosterone release from the adrenal gland directly, and indirectly through activation of the hypothalamic-pituitary-adrenal axis. The aim of this paper was to determine whether IL-1-stimulated corticosterone release occurs indirectly through the local release of catecholamines from the rat adrenal gland. To accomplish this, experiments were conducted on both quartered rat adrenal glands and primary cultures of dispersed adrenal cells. Incubation of quartered adrenals with adrenocorticotropic hormone (ACTH, 10(-12) to 10(-8) M) or IL-1beta (10(-12) to 10(-8) M) resulted in dose-dependent increases (P < 0.05) in corticosterone release. Corticosterone release stimulated by 10(-8) M doses of ACTH and IL-1beta began to rise 30 min after incubation and peaked at 2 h. In primary cultures of adrenal cells, IL-1alpha and IL-1beta elevated corticosterone release after a 24-h incubation period. ACTH elevated corticosterone levels at 4 and 24 h. The stimulatory effect of IL-1 on corticosterone release was mimicked by epinephrine (10(-6) M), and was selectively blocked by the alpha-adrenergic antagonist phentolamine (10(-5) M). The beta-adrenergic antagonist propranolol (10(-5) M) did not change IL-1-induced corticosterone release. Neither phentolamine nor propranolol had an effect on ACTH-stimulated corticosterone release. Both IL-1alpha and IL-1beta significantly increased (P < 0.05) epinephrine levels after a 24-h incubation period compared with media-treated controls. These observations suggest that locally released catecholamines mediate the stimulatory effect of IL-1 on corticosterone release through an alpha-adrenergic receptor in the rat adrenal gland.