DEXAMETHASONE AND METHYLPREDNISOLONE AFFECT RAT PERITONEAL PHAGOCYTE CHEMILUMINESCENCE AFTER ADMINISTRATION IN-VIVO

Production of reactive oxygen compounds by peritoneal monocytes/macrop hages was studied in rats exposed to dexamethasone or methylprednisolo ne in the drinking water. Luminol-amplified chemiluminescence was meas ured in preparations of peritoneal leukocytes activated ex vivo by ser um opsonized zymosan, N-formyl-L-methionyl-L-leucyl-L-phenylalamine (f MLP) or phorbol 12-myristate 13-acetate (PMA). After dexamethasone adm inistration for 1 day (similar to 0.13 mg/kg per 24 h) a significant r eduction in chemiluminescence was found in cells stimulated with serum opsonized zymosan, while responses to fMLP and PMA stimulation were s ignificantly reduced after 2 days. The maximal inhibition obtained aft er 5-8 days of dexamethasone administration (plasma levels < 5 nM) was 92.0 +/- 1.2%, 87.6 +/- 0.2% and 84.5 +/- 3.1% in cells stimulated wi th serum opsonized zymosan, fMLP and PMA, respectively. Administration of dexamethasone or methylprednisolone for 48 h gave a dose-dependent reduction of chemiluminescence. ED(50) values of dexamethasone were e stimated at 0.06-0.15 mg/kg for the different stimulators (plasma conc entrations 5-10 nM). Estimated ED(50) values for methylprednisolone we re 35-36 mg/kg. Since the percentage of mononuclear phagocytes in the peritoneal cell population did not change significantly with dose or t ime of dexamethasone exposure, this study indicates that glucocorticoi ds have a depressive effect on the monocyte/macrophage 'respiratory bu rst' in vivo. The results are consistent with the hypothesis that thes e effects are mediated by glucocorticoid receptors. Although the pathw ay activated by serum opsonized zymosan was more rapidly inhibited tha n the fMLP- and PMA-activated pathways, the responses induced by the d ifferent stimulators were similarly affected, suggesting a modulation of common components in the activation pathways, possibly protein kina se C or the NADPH-oxidase complex, after administration of low pharmac ological doses of glucocorticoids in vivo.