HUMAN ADRENAL-CELLS EXPRESS TUMOR-NECROSIS-FACTOR-ALPHA MESSENGER-RIBONUCLEIC-ACID - EVIDENCE FOR PARACRINE CONTROL OF ADRENAL-FUNCTION

Tumor necrosis factor (TNF) is gaining increasing importance in clinic al medicine. It plays a role in the interaction of the immune system w ith the hypothalamic-pituitary-adrenal axis. In the present study vari ous morphological methods, including immunohistochemistry, electron mi croscopy, and in situ hybridization were applied to characterize the l ocalization and distribution of TNF in the human adrenal gland. Double immunostaining revealed an astonishing degree of intermingling of ste roid-producing cells and chromaffin cells. Macrophages could be found in all regions of the adrenal gland, but particularly in the transitio n zone of cortex and medulla. The steroid-producing cells of the inner zone of the cortex express major histocompatibility complex class II molecules. On the ultrastructural level, immune cells, steroid cells, and catecholamine-producing cells were found in direct contact. The co mbination of immunohistochemistry and in situ hybridization was optima lly suited to define the exact cellular source of TNF in the human adr enal. TNF is produced in macrophages, but above all in 17 alpha-hydrox ylase-positive cells (steroid-producing cells) in the zona reticularis and medulla. No signal was found in chromaffin cells. TNF may induce major histocompatibility complex class II in human adrenal gland in a paracrine or autocrine manner. It is concluded that TNF may have an im portant role in normal human adrenal physiology.