The Endothelium Secretes Interleukin-6 (IL-6) and Induces IL-6 and Aldosterone Generation by Adrenocortical Cells

Endothelial cells have been shown to induce adrenal steroidogenesis and to enhance aldosterone secretion via angiotensin II and endothelin-1-independent mechanisms. It has been demonstrated that endothelial cells and adrenocortical cells are capable of producing interleukin-6 (IL-6) and IL-6 is a factor known to stimulate adrenal cortisol secretion. We therefore asked whether endothelial cells have an effect on adrenal IL-6 generation and whether IL-6 mediates biosynthesis of aldosterone as is observed after exposure of adrenocortical cells to endothelial cell-conditioned medium (ECCM). Cells from the adrenocortical cancer cell line NCl-H295R were incubated with ECCM produced from human Umbilical vein endothelial cells at increasing concentrations. As detected by an enzyme-linked immunosorbent assay, pure ECCM significantly increased IL-6 protein secretion by Cultured adrenocortical cells in a dose-dependent fashion, to a 18.0 +/- 2.0 pg/mL (mean +/- SEM). This was paralleled by an enhanced IL-6 promoter activity as determined with the transfection of an IL6-promoter-luciferase reporter gene Construct. Pure ECCM also induced aldosterone secretion by adrenocortical cells more than three times that of controls with serum-free medium. ECCM per se contains significant amounts of IL-6 protein. However, blockade of IL-6 signal transduction did not interfere with aldosterone synthesis. These data suggest that endothelial cells secrete IL-6 and that endothelial cell-derived factors regulate adrenal IL-6 synthesis which does not alter adrenal aldosterone secretion. Our findings Support the hypothesis that the endothelium and the adrenal gland may play a role in the development of some forms of hypertension and - more speculative - inflammation.