Modulation of IL-18 production in the adrenal cortex following acute ACTH or chronic corticosterone treatment

Interleukin (IL)-18 is a proinflammatory cytokine and a stimulator of cell- mediated immune responses. We have previously reported that acute stress st imulates the production of IL-18 mRNA in the glucocorticoid (GC)-producing cells of the adrenal cortex. In order to investigate the mechanisms governi ng the expression of IL-18 in the adrenal cortex, the effects of acute ACTH or ch Tonic corticosterone treatment on the levels of IL-18 mRNA and prote in were examined by in situ hybridization and Northern and Western blot ass ays. Adult male Sprague-Dawley rats received a subcutaneous injection of AC TH or subcutaneous implantation of slow-release corticosterone pellets foll owed by an injection of saline or ACTH. After 4 h, ACTH induced a 4-fold in crease in IL-18 mRNA levels and elevated the content of pro-IL-18 peptide. Six days of chronic corticosterone treatment did not alter the basal levels of IL-18 mRNA and reduced those of pro-IL-18, Finally, ACTH treatment of a nimals under the corticosterone regimen induced a 2-fold increase in IL-18 mRNA and elevated the levels of the pro-IL-18 protein. The levels of the pr ecursor, p45, and the active subunit p10 peptides of the IL-18-processing e nzyme, IL-1 beta-converting enzyme (ICE), showed no substantial differences in all the conditions tested. IL-1 beta was not detected under these exper imental conditions. These data demonstrate that the production of IL-18 in the adrenal cortex is stimulated by ACTH treatment and is not inhibited by the direct action of corticosterone. In contrast to the anti-inflammatory a ction of GCs, IL-18 may have an immunostimulatory role during acute stress. Copyright (C) 2000 S. Karger AG, Basel.