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 stimulates the production of IL-18 mRNA in the glucocorticoid (GC)-producing cells of the adrenal cortex. In order to investigate the mechanisms governing the expression of IL-18 in the adrenal cortex, the effects of acute ACTH or chronic corticosterone treatment on the levels of IL-18 mRNA and protein were examined by in situ hybridization and Northern and Western blot assays. Adult male Sprague-Dawley rats received a subcutaneous injection of ACTH or subcutaneous implantation of slow-release corticosterone pellets followed by an injection of saline or ACTH. After 4 h, ACTH induced a 4-fold increase 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 animals 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 precursor, p45, and the active subunit p10 peptides of the IL-18-processing enzyme, IL-1beta-converting enzyme (ICE), showed no substantial differences in all the conditions tested. IL-1beta was not detected under these experimental 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 action of GCs, IL-18 may have an immunostimulatory role during acute stress.
Conti
B
B
Laboratory of Molecular Neurobiology, Weill Medical College of Cornell University at The Burke Medical Research Institute, White Plains, NY 10605, USA. bconti@burke.org
Sugama
S
S
Kim
Y
Y
Tinti
C
C
Kim
H
H
Baker
H
H
Volpe
B
B
Attardi
B
B
Joh
T
T
D000302:Adrenal Cortex / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003345:Corticosterone / Q000494:pharmacology*; D015870:Gene Expression / Q000276:immunology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000276:immunology; D017403:In Situ Hybridization; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000276:immunology
D020382:Interleukin-18; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone