Objective: To investigate the effects of lovastatin combined with cyclosporine A (CsA) on cultured human peripheral blood mononuclear cells (PBMC) proliferation, cytokines expression and cytotoxicity in vitro.
Methods: The PBMC was isolated by using Ficoll-Hypague density gradient centrifugation method and its viability was evaluated with LDH-release assay. The effects of lovastatin combined with CsA on cultured PBMC proliferation and cytotoxicity were observed in 3H-TdR incorporation assay. The levels of supernatant IFN-gamma and IL-2 were quantitated respectively with RIA and ELISA-SPOT assay. The IL-2 and IFN-gamma mRNA expressions were determined by RT-PCR.
Results: Both lovastatin and CsA inhibited PBMC proliferation, expression of IL-2 and IFN-gamma, and NK cell cytotoxicity in a dose-dependent manner. Combination of the two drugs produced synergism.
Conclusion: Statins combined with cyclosporine A have a synergic effect and can delay the incidence and development of allograft rejection and prolong the graft life-span in animal models and clinical trials.