Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages

Abstract

The effect of glucocorticoids on the production of NO 2 − and NO by the macrophage cell line J774 was investigated. Stimulation of the cells with lipopolysaccharide (LPS) resulted in a time-dependent accumulation of NO 2 − in the medium, reaching a plateau after 48h. Concomitant incubation of the cells for 24h with dexamethasone (0.001–1.0 μM) or hydrocortisone (0.01–10.0 μM) caused a concentration-dependent inhibition of NO 2 − formation. The cytosol of J774 cells stimulated with LPS and IFN-γ produced a time-dependent increase in the release of NO. This was blocked in a concentration-dependent manner by dexamethasone and hydrocortisone, but not progesterone, administered concomitantly with the immunological stimulus. None of these compounds had any effect on the release of NO once the enzyme had been induced. The inhibitory effect of hydrocortisone on NO formation was blocked by cortexolone. These data suggest that part of the anti-inflammatory and immunosuppressive actions of glucocorticoids is due to their inhibition of the induction of the NO synthase.