In Vitro Study: Effect Of Mycophenolate Mofetil And Dexamethasone On Systemic Lupus Erythematosus

To investigate the effect of novel immunosuppressant mycophenolate mofetil(MMF) on Th subsets and apoptosis in the peripheral blood mononuclear cells(PBMCs) from patients with systemic lupus erythematosus at both cellular and molecular level, ABC-ELISA method was utilized to measure the levels of IL-10, IL-12 ,IFN-r, sFas and sFasL in the supernatants of cultured PBMCs from SLE, and three-color cytometry was applied to detect the percentage of CD4IFN- Y IL-10 T, CD4IFN- Y IL-10 T, and CD4IFN- Y IL-10 T subsets of lymphocytes. The percentage of apoptosis was also detected by AV-FITC/PI flow cytometry. Our results show that the levels of IL-10, IL-12, and IFN-y were all significantly elevated in the supernatants of cultured PBMCs from SLE, compared with normal control. While the production of IL-10, IL-12 and IFN-v by PBMCs from SLE both spontaneously and under the stimulation of phytohaemagglutinin (PHA) was significantly reduced by MPA, DEX enhanced the secretion of IL-10. The percentages of CD4IFNY IL-10 T and CD4IFN-Y+IL-10+ T subsets in cultured PBMCs from SLE were significantly increased and MPA could decrease the percentages of all three subsets. In contrast, DEX increased the percentage of CD4ITFN- Y +IL-10+ T subset and decreased the percentage of CD4+IFN- Y +IL-10"T subset. After 48hrs of in vitro culture, the percentage of apoptosis and secretion of sFasL were significantly elevated. MPA and DEX could both significantly reduce the production of sFas and sFasL by and promote apoptosis of SLE PBMCs. While DEX inhibited the production of sFas by and induced apoptosis of SLE PBMCs to a higher extent, MPA reduced the production of sFasL more. Our results may offer new insight into the mechanism of efficacy of combined immunosuppressive therapy in SLE, and provide somelaboratory proof and reference for the clinical application of MPA and DEX.