Immunosuppression in human peripheral blood T lymphocytes by fluvastatin.
To investigate the immunosuppressive effect of fluvastatin on the PHA-activated T lymphocytes. T lymphocytes were isolated from the blood of healthy volunteers, cell proliferation and the activation markers expression were examined by flow cytometric analysis. Cytokine secretion was assayed by ELISA. LDH-release assay was used to detect activity of killer cells. NFAT activation was evaluated by TransAM ELISA kit. Results were as following. (1) Whereas no modification in CD25 expression was seen, fluvastatin at 5 microM caused a lower level of CD69 expression, accompanied by an essential suppression on proliferation, IL-2 production and cytotoxicity development in PHA-stimulated T cells. However, the level of secreted IL-10 had no change, and the level of IL-4 even experienced a significant increase. (2) Combined with cyclosporine A (CsA), fluvastatin would further repress CD69 expression, cells proliferation and activity of killer cells, meanwhile significantly induced the secretion of IL-4 and IL-10. (3) Fluvastatin treatment also resulted in a strong inhibition of NFAT activation. In conclusion, partly involving the blockage of activation of NFAT, fluvastatin exhibited an immunosuppressive effect in vitro.
Wu
Li-Hua
LH
Institute of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Wan
Yun-Le
YL
Xie
Hai-Yang
HY
Zhang
Wen-Jin
WJ
Zheng
Shu-Sen
SS
D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology*; D005229:Fatty Acids, Monounsaturated / Q000276:immunology* / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007211:Indoles / Q000276:immunology* / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D000077340:Fluvastatin