Nuovi agenti immunosoppressori nel trapianto

Among the more recent immunosuppressive agents, Sirolimus and monoclonal antibodies directed against the IL-2 receptor are the most promising. Sirolimus inhibits the G₁-S phase of the cell cycle, at a later stage than calcineurin inhibitors, which interfere with the G₀-G₁ phase. Clinical studies have demonstrated the efficacy of Sirolimus in reducing the risk of rejection when combined with CsA and steroids. Sirolimus also proved to be effective as an alternative to CsA. The monoclonal antibodies directed against the IL-2 receptor significantly reduce the risk of acute rejection without side-effects. Other immunosuppressive agents are still being assessed in phase I-H clinical studies. FTY 720 may induce selective apoptosis of lymphocytes reacting against the donor's alloantigens. Antisense oligonucleotides interfere with adhesion molecules, while the monoclonal antibodies CTLA4-Ig and 5C-8 interfere with the co-stimulatory signals between the antigen presenting cell and the lymphocyte. An ever increasing number of new immunosuppressive agents is becoming available. The difficult task of the clinician is to find the right equilibrium in dosing and associating these new drugs in order to maximize the therapeutic effect of immunosuppressive treatment.