Interleukin-4 increases cortisol release and decreases adrenal androgen release from bovine adrenal cells

ACTH is the primary regulator of adrenal function during acute stress. However, during chronic inflammatory stress additional factors play a major role in the regulation of adrenal secretion. Many cytokines circulate in the blood and are synthesized and released from adrenal tissue. Furthermore, these peptides modify adrenal function. Recently, interleukin-4 (IL-4) was demonstrated to be released from a human adrenal tumor cell line. Therefore, we hypothesized that normal bovine adrenocortical cells could express IL-4 and that this cytokine may modify adrenal function. We determined that IL-4 and IL-4 receptors (IL-4R) are expressed in the bovine adrenal cortex whereas the expression of IL-4 and IL-4R in the adrenal medulla was not apparent. Exposure of dispersed bovine adrenocortical cells isolated from the zona fasciculate to IL-4 did not modify basal release of cortisol. However, the ACTH-stimulated release of cortisol from the bovine adrenal cells was augmented by IL-4. IL-4 exposure had no affect on adrenal androgen release from bovine zona reticularis cells, but IL-4 inhibited the ACTH-stimulated release of adrenal androgens from these cells. The effects of IL-4 on ACTH-stimulated cortisol and adrenal androgen release were dependent upon the IL-4 incubation interval and the IL-4 concentration. Because communication between the immune and endocrine systems is important in inflammatory conditions, IL-4 may play a role in coordinating the adrenal response to inflammatory stress.