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Organ Transplantation

Graft Rejection
    Cellular Mechanisms
    Molecular Mechanisms

Immunsuppressive Agents
    Corticosteroids
    Calcineurine Inhibitors
    Antiproliferative Agents
    Monoclonal Antibodies
    Polyclonal Antibodies
    Side Effects       

Immunotherapy
    Inductive Therapy
    Maintenance Therapy
    Episodic Treatment

Current Areas of Research
    New Drugs
    Drug Efficacy
    Alternative Therapies
        Tolerance
        Tissue Engineering
        Xenotransplantation

Glossary of Terms
References

IMMUNOSUPPRESSIVE AGENTS

"There are few examples of clinical procedures that have moved from complete failure to outstanding success in such a short space of time (Parrot)." Organ transplantation therapy is one of those examples. The human HLA antigen proved such a barrier to organ grafting "that prior to the late 1950's, transplantation yielded uniformly dismal and consistently fatal results (Lysaght)." It was only through the discovery, evolution, and routing use of immunosuppressant agents that this barrier has finally been overcome. In fact, many organ transplantations are now routine clinical procedures - the kidney transplant is a prime example, with 15,122 procedures performed in 2003. Organ transplantation therapy is highly dependent on the success of pharmacotherapy to suppress recipient immune responses to the foreign organ; allograft rejection remains as the major barrier to long-term graft survival in patients. In fact, transplant patients require lifelong immunosuppressive drug therapy to prevent this rejection.

Despite these glamorous advances, it is important to bear in mind the mechanism behind immunosuppression: immunosuppressants dampen the body's immune system. With current therapy, there are adverse side-effects that include, among others, a high incidence of opportunistic infection and transplant-related malignancies in patients. These are the unfortunate consequences of overimmunosuppression. Accordingly, a major goal of immunosuppression is to identify the optimal balance of therapy such that there is effective prevention of allograft rejection, while drug-related adverse effects, infection, and malignancies are minimized. Because this compromise is largely unsatisfactory, there is a constant search for more effective and specific immunosuppressive agents and strategies.

Five basic categories of immunosuppressive agents are used in organ transplantation: corticosteriods, calcineurine inhibitors, antiproliferative agents, monoclonal antilymphocyte antibodies, and polyclonal antilymphocyte antibodies. Each type works to block a particular step of rejection. Also included are pages concerning drug efficacy and side effects.