GLUCOCORTICOIDS INHIBIT APOPTOSIS OF HUMAN NEUTROPHILS

Human neutrophils rapidly undergo apoptotic cell death, Because glucoc orticoids are known to modulate an array of neutrophil functional acti vities as well as induce rapid apoptosis in susceptible lymphocyte pop ulations, we have examined the effects of glucocorticoids on apoptosis in mature human neutrophils. In cultures of neutrophils maintained in vitro, the glucocorticoids, dexamethasone, 6 alpha-methylprednisolone , and hydrocortisone, inhibited the development of apoptotic morpholog y by 59% to 90% when assessed at 12, 24, and 48 hours. In contrast, co rticosteroids lacking anti-inflammatory activity and progesterone fail ed to affect development of the morphologic features of apoptosis. The concentration of dexamethasone required to reduce apoptosis by 50% at 24 hours was approximately 5 x 10(-8) mol/L, a concentration that is achievable in plasma after dexamethasone treatment. Dexamethasone (10( -6) mol/L), but not progesterone, reduced the percentage of hypodiploi d (apoptotic) nuclei by 40% to 90% over this time course. Similarly, d examethasone reduced the DNA cleavage associated with apoptosis and pr olonged the viability of neutrophils maintained in culture for 12 to 4 8 hours. Glucocorticoid-mediated modulation of neutrophil apoptosis wa s qualitatively similar, but lesser in magnitude, when compared with t he effects of granulocyte colony-stimulating factor (100 ng/mL). Thus, glucocorticoids exert a protective effect on human neutrophil surviva l by delaying apoptosis. (C) 1995 by The American Society of Hematolog y.