INTERLEUKIN-3 AND INTERLEUKIN-6 STIMULATE CORTISOL SECRETION FROM ADULT HUMAN ADRENOCORTICAL-CELLS

Accumulating data indicate that interleukins can activate the hypothal amic-pituitary-adrenal (HPA) axis. We evaluated the effect of human re combinant interleukin-3 (IL-3) and interleukin-6 (IL-6) on cortisol se cretion from adult human adrenocortical cells in primary culture. IL-3 and IL-6 (100 mu g/L) equipotently stimulated basal cortisol secretio n approximately 5-fold. The stimulatory effect was significant after 1 2 h (p<0.01) and maximum cortisol levels were induced after 48 h. In c ontrast to ACTH, which significantly induced cAMP levels in parallel t o its steroidogenic effect, IL-3 or IL-6 had no significant effect on cAMP. Furthermore, we showed that specific inhibition of the cyclooxyg enase pathway by indomethacin completely blocked the steroidogenic eff ect of IL-6 while the effect of IL-3 was not affected. In contrast, co incubation with nordihydroguaiaretic acid - a specific inhibitor of th e lipoxygenase system - abolished IL-3 stimulated steroidogenesis but had no effect on IL-6 stimulated cortisol secretion. These findings in dicate that IL-3 and IL-6 directly stimulate the steroidogenesis at th e adrenal level through activation of different, cAMP-independent path ways. While the stimulatory effect of IL-6 on cortisol secretion from adult human adrenocortical cells seems to be mediated through the cycl ooxygenase pathway, the effect of IL-3 on adrenocortical cortisol secr etion is dependent on the lipoxygenase pathway.