Stimulation by interleukin-6 and inhibition by tumor necrosis factor of cortisol release from bovine adrenal zona fasciculata cells through their receptors

Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are synthe sized and released from adrenal cells. Therefore, the effects of TNF-alpha and IL-6 on cortisol release from bovine zona fasciculata (ZF) cells were i nvestigated. IL-6 (10-1000 pg/mL) significantly increased basal and adrenoc orticotropic hormone (ACTH)-stimulated cortisol release in a concentration- dependent manner. This stimulatory effect of IL-6 became apparent at interv als as short as 4 h and continued through 24 h. IL-6 also potentiated the c ortisol release stimulated by the adenylyl cyclase activator forskolin. By contrast, TNF-alpha (0.1-10 ng) inhibited basal and ACTH-stimulated cortiso l release in a concentration-dependent manner. The inhibitory effects of TN F-alpha on cortisol release were significant at time intervals as short as 4 h and continued through 24 h. TNF-alpha inhibited forskolin-stimulated co rtisol release. Binding studies demonstrated that ZF cells have IL-6 recept ors (100 receptors/cell, K-d of 7.5 x 10(-11)) and TNF receptors (200 recep tors/cell, K-d of 2.4 x 10(-9) M). Immunohistochemical analysis provided ev idence that the majority of ZF cells have IL-6 receptors, TNF type 1 recept ors, and TNF type 2 receptors. Because IL-6 and TNF-alpha are released from the adrenal cortex and these cytokines modify the release of cortisol from the ZF, IL-6 and TNF-alpha may play a paracrine or autocrine role in the r egulation of adrenal function.