INTERLEUKIN-1 REGULATES CORTICOSTERONE SECRETION FROM THE RAT ADRENAL-GLAND THROUGH A CATECHOLAMINE-DEPENDENT AND PROSTAGLANDIN E(2)-INDEPENDENT MECHANISM

Studies from this and other laboratories have shown that interleukin-1 alpha (IL-1 alpha) stimulates corticosterone and prostaglandin (PG) release from primary cultures of rat adrenal cells. A previous report from our laboratory (1) indicated involvement of the alpha-adrenergic system in IL-1 alpha-stimulated corticosterone secretion from primary cultures of rat adrenal cells. The present experiments were conducted to determine the role of catecholamines and eicosanoids in IL-1-stimulated corticosterone release from primary rat adrenal cells. Primary adrenal cells were incubated for 24 h at 37 C with IL-1 alpha (10 nM), medium, or the appropriate agonist. After incubation, the supernatant was removed and assayed for epinephrine, prostaglandin E(2) (PGE(2)), and corticosterone concentrations. At this time, untreated adrenal cells were fixed for immunohistochemical staining with a specific antirat tyrosine hydroxylase antibody. The results indicate that the primary adrenal cells contained 3.1 +/- 0.45% tyrosine hydroxylase-positive cells. On the ultrastructural level, the chromaffin cells were found to be in direct cellular contact with cortical cells. IL-1 alpha significantly increased (P < 0.05) epinephrine, PGE(2), and corticosterone levels above those in medium-treated controls from primary adrenal cells. In the presence of the alpha-adrenergic antagonist phentolamine (10 mu M), IL-1 alpha-stimulated (P < 0.05) corticosterone release was inhibited, whereas IL-1 alpha-induced PGE(2) release was not affected. Conversely, the presence of the cyclooxygenase inhibitor indomethacin (10 mu M) significantly inhibited IL-1 alpha-induced PGE(2) secretion without altering the effect of IL-1 alpha on corticosterone release. Inhibitors of the 5-lipoxygenase system (10 mu M CGS 8518) and the lipoxygenase and cytochrome P450 monooxygenase systems (10 mu M nordihydroguaiaretic acid) did not effect IL-1 alpha-induced corticosterone or PGE(2) release. These observations indicate that IL-1 alpha stimulates corticosterone release through an alpha-adrenergic mechanism that is independent of PGE(2) release from primary rat adrenal cells.