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-α (TNFα) are synthesized and released from adrenal cells. Therefore, the effects of TNF-α and IL-6 on cortisol release from bovine zona fasciculata (ZF) cells were investigated. IL-6 (10-1000 pg/mL) significantly increased basal and adrenocorticotropic hormone (ACTH)-stimulated cortisol release in a concentration-dependent manner. This stimulatory effect of IL-6 became apparent at intervals as short as 4 h and continued through 24 h. IL-6 also potentiated the cortisol release stimulated by the adenylyl cyclase activator forskolin. By contrast, TNF-α (0.1-10 ng) inhibited basal and ACTH-stimulated cortisol release in a concentration-dependent manner. The inhibitory effects of TNF-α on cortisol release were significant at time intervals as short as 4 h and continued through 24 h. TNF-α inhibited forskolin-stimulated cortisol release. Binding studies demonstrated that ZF cells have IL-6 receptors (100 receptors/cell, K_d of 7.5 × 10^-11) and TNF receptors (200 receptors/cell, K_d of 2.4 × 10^-9 M). Immunohistochemical analysis provided evidence that the majority of ZF cells have IL-6 receptors, TNF type receptors, and TNF type 2 receptors. Because IL-6 and TNF-α are released from the adrenal cortex and these cytokines modify the release of cortisol from the ZF, IL-6 and TNF-α may play a paracrine or autocrine role in the regulation of adrenal function.