EFFECTS OF GLUCOCORTICOIDS ON APOPTOSIS OF INFILTRATED EOSINOPHILS AND NEUTROPHILS IN RATS

The effects of glucocorticoids on the survival of rat eosinophils and neutrophils infiltrated into the peritoneal cavity were examined. Gluc ocorticoids including dexamethasone, prednisolone and hydrocortisone i nhibited the survival of rat peritoneal eosinophils at 10(-6) M, where as they prolonged survival of rat peritoneal neutrophils at 10(-8) M. Sex steroids including estradiol and progesterone did not affect cell survival. Dexamethasone decreased the viability of eosinophils after 3 days of incubation and maintained the viability of neutrophils until 4 days after incubation concentration dependently. The EC50 of dexamet hasone for inhibition of the survival of eosinophils was 1.5 x 10(-8) M, and that for the spontaneous death of neutrophils was 6.4 x 10(-10) M, suggesting that glucocorticoids at concentrations that inhibit eos inophil survival prolong neutrophil survival. Analysis of DNA fragment ation of cultured eosinophils and neutrophils revealed that glucocorti coids enhance eosinophil apoptosis but inhibit neutrophil apoptosis. T he effects of dexamethasone on viability and DNA fragmentation were co unteracted by the glucocorticoid receptor antagonist, mifepristone, co ncentration dependently. These findings indicate that glucocorticoids induce contradictory effects via the glucocorticoid receptor on rat eo sinophils and neutrophils extravasated to an inflammatory locus such a s the peritoneal cavity by modulating apoptosis. (C) 1998 Elsevier Sci ence B.V. All rights reserved.