DOSE-DEPENDENT AND TIME-DEPENDENT ACTIVATION OF RAT ALVEOLAR MACROPHAGES BY GLUCOCORTICOIDS

Effects of glucocorticoids on immune functions are generally thought t o be suppressive and antiinflammatory. However, most reports dealing w ith this issue describe effects of long-term treatment with high doses of glucocorticoids on immune functions. In the present study we have investigated both dose and timing effects of exposure of alveolar macr ophages with dexamethasone on lipopolysaccharide (LPS)-induced IL-I be ta and nitric oxide secretion. For this purpose, alveolar macrophages were preincubated with various doses of dexamethasone during varying i ntervals, followed by stimulation of the cells with endotoxin, either in the absence or presence of dexamethasone. Subsequently, the effects of this treatment on IL-I beta and nitric oxide secretion were measur ed. It was shown that both short-term incubation of alveolar macrophag es with high doses of dexamethasone and long-term incubation with low doses of dexamethasone lead to enhanced nitric oxide and enhanced IL-1 beta secretion upon subsequent stimulation of the cells with LPS. In contrast, long-term incubation of alveolar macrophages with high-dose dexamethasone leads to decreased IL-I beta and nitric oxide secretion upon subsequent stimulation. Thus, it is concluded that the effects of dexamethasone on rat alveolar macrophages are both time- and dose-dep endent. It is therefore argued that effects of glucocorticoids on immu ne functions are not a priori suppressive, but that both dose and timi ng effects should be taken into account.