Assist. Professor

Dr. Abdulrahman M. Geeran Al Fahdawi

Ph.D. Clinical Immunology

Mitotic inhibitors in successful transplantation

A variety of immunosuppressive agents can aid in the survival of the transplants, including drugs and specific antibodies developed to diminish the immunologic attack on grafts. One of the most important agents is mitotic inhibitors.

Azathioprine (Imuran), a potent mitotic inhibitor, is often given just before and after transplantation to diminish T-cell proliferation in response to the alloantigens of the graft. Azathioprine acts on cells in the S phase of the cell cycle to block synthesis of inosinic acid, which is a precursor of the purines adenylic and guanylic acid. Both B-cell and T-cell proliferation is diminished in the presence of azathioprine. Functional immune assays such as the MLR, CML, and skin test show a significant decline after azathioprine treatment, indicating an overall decrease in T-cell numbers. Two other mitotic inhibitors that are sometimes used in conjunction with other immunosuppressive agents are cyclophosphamide and methotrexate. Cyclophosphamide is an alkylating agent that inserts into the DNA helix and becomes cross-linked, leading to disruption of the DNA chain. It is especially effective against rapidly dividing cells and therefore is sometimes given at the time of grafting to block T-cell proliferation. Methotrexate acts as a folic-acid antagonist to block purine biosynthesis.