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 mumol L-1 and with adrenocorticotropic hormone (ACTH) up to 100 micrograms mL-1. The monocyte/macrophage production of reactive oxygen molecules was measured by luminol amplified chemiluminescence, and the production of nitric oxide (NO) was measured as nitrite (NO2-). Dexamethasone in vitro in nanomolar concentrations inhibited monocyte/macrophage chemiluminescence and also nitric oxide production; the potency was dexamethasone > methylprodnisolone > prednisolone. ACTH enhanced both activated chemiluminescence and endotoxin-induced nitric oxide production, but only at concentrations about 20-100 micrograms mL-1, and there was no significant effect of physiological concentrations. In summary, the results of the present study further confirm and substantiate that glucocorticoids in low pharmacological concentrations have a general inhibitory effect on monocyte/ macrophage production of reactive oxygen molecules through the specific glucocorticoid receptors, while the stimulatory effect of ACTH is only observed by very high, non-physiological concentrations. Furthermore, since low concentrations of glucocorticoids inhibited the production of these reactive oxygen molecules in vitro, indirect mechanisms involving hormones and other elements outside the immune system are not essential for the effect of glucocorticoids on monocytes/macrophages.
Haugen
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Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller, Norway.
Wiik
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D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D008163:Luminescent Measurements; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D009195:Peroxidase / Q000037:antagonists & inhibitors; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D011921:Rats, Inbred WKY; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D002273:Carcinogens; D005938:Glucocorticoids; D009573:Nitrites; D009569:Nitric Oxide; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate