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ISSN 1672-9145 Acta Biochim Biophys Sin 2004, 36(10): 649–655 CN 31-1940/Q

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Immunosuppression in Human Peripheral Blood T Lymphocytes by Fluvastatin

Li-Hua WU, Yun-Le WAN¹, Hai-Yang XIE, Wen-Jin ZHANG, and Shu-Sen ZHENG*

Institute of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China;

¹Centre of organ transplantation, The Second Affiliated Hospital, School of Medicine, Zhongshan University, Guangzhou 510000, China

Abstract 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 TransAMTM ELISA kit. Results were as following. (1) Whereas no modification in CD25 expression was seen, fluvastatin at 5 mM 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.

Key words fluvastatin; T cell activation; T cell proliferation; cytokine; nuclear factor of activated T lymphocytes

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Received: June 14, 2004 Accepted: August 31, 2004

This work was supported by the grants from the Major State Basic Research Development Program of China (No. 2003CB515501) and the Academician Foundation of Zhejiang Science and Technology Bureau (No. 2003A1008-07)

*Corresponding author: 86-571-87236570; E-mail, [email protected]