GLUCOCORTICOID AND ACTH REGULATION OF RAT PERITONEAL PHAGOCYTE CHEMILUMINESCENCE AND NITRIC-OXIDE PRODUCTION IN CULTURE

In order to study the adrenocortical regulation of monocyte/macrophage functions further, leucocytes from the rat peritoneum were incubated in vitro with glucocorticoid concentrations up to 10 mu mol L-1 and wi th adrenocorticotropic hormone (ACTH) up to 100 mu g mL(-1). The monoc yte/macrophage production of reactive oxygen molecules was measured by luminol amplified chemiluminescence, and the production of nitric oxi de (NO) was measured as nitrite (NO2-). Dexamethasone in vitro in nano molar concentrations inhibited monocyte/macrophage chemiluminescence a nd also nitric oxide production; the potency was dexamethasone > methy lprodnisolone > prednisolone. ACTH enhanced both activated chemilumine scence and endotoxin-induced nitric oxide production, but only at conc entrations about 20-100 mu g mL(-1), and there was no significant effe ct of physiological concentrations. In summary, the results of the pre sent study further confirm and substantiate that glucocorticoids in lo w pharmacological concentrations have a general inhibitory effect on m onocyte/macrophage production of reactive oxygen molecules through the specific glucocorticoid receptors, while the stimulatory effect of AC TH is only observed by very high, nonphysiological concentrations. Fur thermore, since low concentrations of glucocorticoids inhibited the pr oduction of these reactive oxygen molecules in vitro, indirect mechani sms involving hormones and other elements outside the immune system ar e not essential for the effect of glucocorticoids on monocytes/macroph ages.