The Effects of Silymarin and Cyclosporine A on the Proliferation and Cytokine Production of Regulatory T Cells

Abstract

Background: Immunosuppressive agents are necessary to enhance allograft tolerance after transplantation and the treatment of autoimmune disorders. Regulatory T cells (Tregs) play a pivotal role in improving allograft tolerance and determining the fate of transplanted organs. Therefore, the aim of this study was to investigate the immunomodulatory effects of cyclosporine A (CsA) and silymarin on the proliferation and cytokine production of Tregs. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from healthy voluntaries and Tregs were isolated using an immunomagnetic separation method. The phenotypic characteristics of Tregs were determined by flow cytometry. Tregs were expanded and then cultured with different concentrations of CsA and silymarin. The effects of CsA and silymarin on the viability, proliferation, and transforming growth factor-beta 1 (TGF-beta1) production of Tregs were determined after 3 and 5 days of culture. Results: CsA significantly decreased Treg proliferation in a dose-dependent manner (p < 0.01-0.05). CsA failed to change TGF-beta1 production of Tregs. On the contrary, silymarin significantly increased the proliferation of Tregs (p < 0.01-0.05). A statistically significant increase was also observed in the TGF-beta1 production of Tregs (p < 0.01-0.05). Our data showed that Treg viability was not compromised by CsA and silymarin. Conclusion: Overall, the results of this study for the first time indicate that silymarin, unlike CsA, has the ability to increase the proliferation and TGF-beta1 production of Tregs and may be beneficial in the treatment of autoimmune disorders and improvement of Treg-dependent allograft tolerance after transplantation.