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, Kd of 7.5 × 10-11) and TNF receptors (200 receptors/cell, Kd 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.
Bibliographical noteFunding Information:
We wish to express gratitude for the cooperation of the management and workers of the Deseret Meat Company, Spanish Fork, Utah which provided the adrenal tissue for this research. We thank the Brigham Young University College of Biological and Agricultural Sciences and the Department of Zoology for the Professional Development Grant that funded this research.
- Cytokine receptors
- Tumor necrosis factor-α