GLUCOCORTICOIDS AND CYCLOSPORINE INDUCE APOPTOSIS IN MITOGEN-ACTIVATED HUMAN PERIPHERAL MONONUCLEAR-CELLS

Induction of apoptosis by immunosuppressive agents such as glucocortic oids (GCs) and cyclosporine (CsA) in cultured lymphoid cells has been suggested. However, there are few studies which demonstrate the induct ion of apoptosis by these agents in the activation process of human pe ripheral blood mononuclear cells (PBMCs). Here we show that potent imm unosuppressive GCs and CsA induce apoptosis in concanavalin A !con Al- activated human PBMCs. In this study, GCs and CsA suppressed human PBM C-blastogenesis when activated by con A in a dose-dependent manner, wh ere healthy PBMCs treated with > 100 ng/ml of each immunosuppressive a gent exhibited a DNA-ladder structure in electrophoretic analysis. In three chronic renal failure (CRF) patients, dose-dependency of the PBM C-apoptosis induction was confirmed by our quantification of fragmente d DNA using ELISA. Furthermore, the enrichment of DNA fragmentation wa s significantly associated with the rate of PBMC-blastogenesis when tr eated with GCs or CsA (r=-0.466, P<0.01). These results suggested that suppression of the mitogen-induced PBMC-blastogenesis by the immunosu ppressive agents should be correlated with the induction of apoptosis.