How does cyclosporine contribute to immunosuppression following liver transplantation?

Updated: Dec 31, 2017
  • Author: Lemi Luu, MD, RDMS, FACEP, FAAEM; Chief Editor: Barry E Brenner, MD, PhD, FACEP  more...
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Answer

Answer

Cyclosporine (cyclosporine A) is a cyclic polypeptide immunosuppressant derived from the fungus Beauvaria nivea. Cyclosporine achieves its effects through reversible inhibition of immunocompetent lymphocytes in the G0 and G1 phases of cell division. T-helper cells are the primary targets of the drug, although T-suppressor cells may be affected. Cyclosporine also works by inhibiting calcineurin and thereby impairing interleukin 2 (IL-2) transduction. Since IL-2 is crucial to the recruitment and activation of T-helper cells and is one of the major determinants of the magnitude of the immune response to a donor allograft, blocking its production profoundly influences the rejection process.

Elimination is primarily biliary, with some excretion into the urine. Cyclosporine is dosed according to blood levels and renal function. The dose is highly individualized because of variable absorption, elimination, and effect on renal function. The drug is initiated at 1-2 mg/kg/day in two divided doses and advanced as tolerated, but the maintenance dosage ranges widely, from 1-10 mg/kg/day.

Such target dosing levels are developed by various centers primarily on the basis of experience, given that no clear correlation has been seen between level and immunosuppressive activity. Generally, the 2-hour postdose level is measured and is believed to reflect immunosuppression  better than the trough level does.


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