Glucocorticoids and cyclosporine induce apoptosis in mitogen-activated human peripheral mononuclear cells.
Induction of apoptosis by immunosuppressive agents such as glucocorticoids (GCs) and cyclosporine (CsA) in cultured lymphoid cells has been suggested. However, there are few studies which demonstrate the induction of apoptosis by these agents in the activation process of human peripheral blood mononuclear cells (PBMCs). Here we show that potent immunosuppressive GCs and CsA induce apoptosis in concanavalin A (con A)-activated human PBMCs. In this study, GCs and CsA suppressed human PBMC-blastogenesis when activated by con A in a dose-dependent manner, where healthy PBMCs treated with > 100 ng/ml of each immunosuppressive agent exhibited a DNA-ladder structure in electrophoretic analysis. In three chronic renal failure (CRF) patients, dose-dependency of the PBMC-apoptosis induction was confirmed by our quantification of fragmented DNA using ELISA. Furthermore, the enrichment of DNA fragmentation was significantly associated with the rate of PBMC-blastogenesis when treated with GCs or CsA (r = -0.466, P < 0.01). These results suggested that suppression of the mitogen-induced PBMC-blastogenesis by the immunosuppressive agents should be correlated with the induction of apoptosis.
Horigome
A
A
Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Hirano
T
T
Oka
K
K
Takeuchi
H
H
Sakurai
E
E
Kozaki
K
K
Matsuno
N
N
Nagao
T
T
Kozaki
M
M
D017209:Apoptosis / Q000187:drug effects*; D003208:Concanavalin A / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D004247:DNA / Q000032:analysis / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004586:Electrophoresis; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens / Q000494:pharmacology*; D013268:Stimulation, Chemical
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D008934:Mitogens; D003208:Concanavalin A; D016572:Cyclosporine; D004247:DNA