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[Immunosuppressive agents in organ transplantation]
S Bergan1, D Albrechtsen, O Bentdal
1Institutt for klinisk biokjemi, Rikshospitalet, Oslo.
Initial use of intensive immunosuppressive therapy is mandatory after organ transplantation; during the following months treatment is tapered to the lowest effective and tolerable maintenance level. Immunosuppressants with different mechanisms of action are combined in order to obtain additive or synergistic effects, and to reduce the incidence of adverse effects. Traditional immunosuppressive agents like azathioprine, steroids, cyclosporine and polyclonal and monoclonal antibodies against T-cell antigens are challenged by new drugs like mycophenolate mofetil, tacrolimus, sirolimus and interleukin-2 receptor monoclonal antibodies. A combination of the most potent drugs could induce nearly complete immunosuppression. Such treatment, however, is a delicate balance between rejection due to poor immunosuppression on one side and, on the other, infections and malignancies induced by overtreatment. According to current protocols, therapeutic drug monitoring is used to individualize the dosage of immunosuppressants and as a means to control the tapering of these drugs. Validation of new immunosuppressive agents should be based on data from long-term studies including patient survival and graft function and survival as endpoints. Among the most recent achievements, inhibitors of costimulatory signaling in T-cells are of clinical interest since they may induce donorspecific tolerance and thereby alleviate the need for life-long maintenance immunosuppressive therapy.
Initial use of intensive immunosuppressive therapy is mandatory after organ transplantation; during the following months treatment is tapered to the lowest effective and tolerable maintenance level. Immunosuppressants with different mechanisms of action are combined in order to obtain additive or synergistic effects, and to reduce the incidence of adverse effects. Traditional immunosuppressive agents like azathioprine, steroids, cyclosporine and polyclonal and monoclonal antibodies against T-cell antigens are challenged by new drugs like mycophenolate mofetil, tacrolimus, sirolimus and interleukin-2 receptor monoclonal antibodies. A combination of the most potent drugs could induce nearly complete immunosuppression. Such treatment, however, is a delicate balance between rejection due to poor immunosuppression on one side and, on the other, infections and malignancies induced by overtreatment. According to current protocols, therapeutic drug monitoring is used to individualize the dosage of immunosuppressants and as a means to control the tapering of these drugs. Validation of new immunosuppressive agents should be based on data from long-term studies including patient survival and graft function and survival as endpoints. Among the most recent achievements, inhibitors of costimulatory signaling in T-cells are of clinical interest since they may induce donorspecific tolerance and thereby alleviate the need for life-long maintenance immunosuppressive therapy.