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) r elease from primary cultures of rat adrenal cells. A previous report f rom our laboratory (1) indicated involvement of the alpha-adrenergic s ystem in IL-1 alpha-stimulated corticosterone secretion from primary c ultures of rat adrenal cells. The present experiments were conducted t o determine the role of catecholamines and eicosanoids in IL-1-stimula ted corticosterone release from primary rat adrenal cells. Primary adr enal cells were incubated for 24 h at 37 C with IL-1 alpha (10 nM), me dium, or the appropriate agonist. After incubation, the supernatant wa s removed and assayed for epinephrine, prostaglandin E(2) (PGE(2)), an d corticosterone concentrations. At this time, untreated adrenal cells were fixed for immunohistochemical staining with a specific antirat t yrosine hydroxylase antibody. The results indicate that the primary ad renal cells contained 3.1 +/- 0.45% tyrosine hydroxylase-positive cell s. On the ultrastructural level, the chromaffin cells were found to be in direct cellular contact with cortical cells. IL-1 alpha significan tly increased (P < 0.05) epinephrine, PGE(2), and corticosterone level s above those in medium-treated controls from primary adrenal cells. I n the presence of the alpha-adrenergic antagonist phentolamine (10 mu M), IL-1 alpha-stimulated (P < 0.05) corticosterone release was inhibi ted, whereas IL-1 alpha-induced PGE(2) release was not affected. Conve rsely, the presence of the cyclooxygenase inhibitor indomethacin (10 m u M) significantly inhibited IL-1 alpha-induced PGE(2) secretion witho ut altering the effect of IL-1 alpha on corticosterone release. Inhibi tors of the 5-lipoxygenase system (10 mu M CGS 8518) and the lipoxygen ase and cytochrome P450 monooxygenase systems (10 mu M nordihydroguaia retic acid) did not effect IL-1 alpha-induced corticosterone or PGE(2) release. These observations indicate that IL-1 alpha stimulates corti costerone release through an alpha-adrenergic mechanism that is indepe ndent of PGE(2) release from primary rat adrenal cells.