KAT45 human pheochromocytoma cell line. A new model for the in vitro study of neuro-immuno-hormonal interactions.

Normal rodent adrenal chromaffin cells and the PC12 rat pheochromocytoma cell line produce IL-1 cytokines. The role, if any, of these cytokines is currently unknown. In PC12 cells, they induce the expression of the L-AA decarboxylase mRNA, a major step in the biosynthesis of catecholamines. Very little if any of these cytokines are detectable in normal human adrenal medulla, being confined mainly in the 17 alpha-hydroxylase-positive steroid cells of the zona reticularis. The aim of the present work was to find out if human pheochromocytomas produce IL-1 cytokines, in vitro, and to examine what local role they may exert. As a model, we have used the new KAT45 cell line, which emerged spontaneously from a primary human pheochromocytoma cell culture. We have found that the KAT45 cells secrete IL-1 beta at 47.8 +/- 9 pg/mg total cellular protein (n = 7, at 24 hours). IL-1 beta increased the concentration of norepinephrine in the KAT45 culture medium from 24.2 +/- 3.5 micrograms/mg protein (n = 6 controls, at 24 hours), to 33.2 +/- 3.5 (IL-1 beta 10 mg/ml) or to 42.9 +/- 8 (IL-1 beta 30 mg/ml). This effect was blocked by IL-1ra. The KAT45 cells also produce CRH and ACTH. IL-1 beta stimulated the secretion of CRH from 19.2 +/- 4 pg/mg protein (n = 5 at 36 hours) to 38.7 +/- 4, an effect blocked by IL-1ra in excess. IL-1 beta had no effect on ACTH secretion.