Effects of Immunosuppresive Regimens on Plasma Level of Transforming Growth Factor-Beta 1 in Renal Transplant Recipients

Transforming growth factor beta (TGF-B) is a signaling molecule with multiple actions in tissue repair and potent fibrogenic properties. The immunosuppressive and proinflammatory properties of TGFB require low concentrations, while higher concentrations are reqiured to induce fibrosis via inhibition of collagenases and matalloproteinases. Experimental and clinical evidence support the role of TGFB in the development of chronic renal damage, the mechanisms being fibroblast proliferation and extracellular matrix deposition. Calcineurin inhibitors are known to enhance TGFB production in vitro and in vivo, and this has been postulated to have negative effects on the long term graft survival. Cyclosporine has beeen shown to induce TGFB synthesis in vitro and in renal transplant recipients, while tacrolimus seeems to induce less production ogf the fibrogenic cytokine.The aim of the study was to investigated the effects of tacrolimus (TAC), cyclosporine (CsA), and sirolimus (SIR) on TGFB plasma levels in renal transplant recipients. The study shows thet TGFB plasma levels are significantly lower in renal transplant recipients receiving TAC-based therapy in respect to patients immunosuppressed with CsA. TGFB plasma levels in Tac-treated patients are constantly low during the first year after transplantation, have not relationship with acute clinical evvents, and are not related to the amount of TAC administrated to patients. In conclusion this stydy indicate that calcineurin inhibition by cyclosporine ia associated with an increased production of TGFB, a potentially harmful effect on the long-term allograft function. The potent immunosuppressive action of TAC, combined with the less active production of TGFB, has a significant long-term benefit for renal transplant recipients.