Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes.

We examined the direct effects of glucocorticoid treatment on neutrophil survival and function in vitro. Four different glucocorticoids caused a dose-dependent inhibition of apoptosis leading to increased survival of neutrophils. Maximal effects were found with dexamethasone at 10(-6) M, 16.6 +/- 6.2 vs 54.6 +/- 6.9, at 24 h (p < 0.05). Nonglucocorticoid steroids did not modulate apoptosis in neutrophils. Furthermore, the effect was inhibited in a dose-dependent manner by the glucocorticoid antagonist RU 486. Glucocorticoid-treated neutrophils produced significantly more superoxide in response to FMLP than untreated controls (p < 0.05). However, both basal and stimulated superoxide production were less than that found with freshly isolated cells. Such lack of priming or activation by glucocorticoids is in contrast to previous experience when increased survival was accompanied by cell activation. When compared with other stimuli, the effect of glucocorticoids at 24 h was similar to that of LPS but less than that of granulocyte-macrophage colony-stimulating factor (GM-CSF), 52 +/- 4, 57 +/- 6, and 70 +/- 4, respectively (p < 0.05). When added in combination, dexamethasone did not increase survival with LPS, but did augment the effect of GM-CSF, suggesting diversity in the mechanisms by which these stimuli regulate apoptosis. These data indicate that glucocorticoids can augment the effector potential of neutrophils by prolonging their survival and functional responsiveness, and such treatment might be detrimental in vivo because of delay in neutrophil apoptosis and in ultimate clearance of them from tissues.