Transplant Immunosuppression: Calcineurin Inhibitors – Cyclosporine and Tacrolimus

After transplantation, recipient T lymphocytes can recognise donor antigens and activate an immune response against the graft. Cyclosporine and tacrolimus interrupt this response by inhibiting calcineurin, an intracellular enzyme needed for transcription of interleukin-2. With less interleukin-2, T-cell activation and proliferation decrease, reducing the likelihood of rejection. This effect is deliberately immunosuppressive rather than selective for the transplanted organ. The same reduction in immune surveillance increases susceptibility to infection and some malignancies. The drugs also affect renal vascular tone, so the treatment that protects the graft can itself reduce kidney function when exposure is excessive. Both agents are used to prevent graft rejection and to treat acute rejection in adult kidney, liver, heart, and bone-marrow transplantation. The supplied Canadian product information also identifies cyclosporine for severe psoriasis and tacrolimus for rheumatoid arthritis. A patient taking either drug for a non-transplant indication still requires the same attention to interactions, concentrations, renal function, blood pressure, and neurologic effects. Cyclosporine and tacrolimus share the major toxicities, but their adverse-effect profiles are not identical. Cyclosporine is classically associated with hirsutism and gingival overgrowth; alopecia...