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Friday 27 March 2009

Ciclosporin, or cyclosporin (former BAN), is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the patient’s immune system and so the risk of organ rejection.

It has been studied in transplants of skin, heart, kidney, liver, lung, pancreas, bone marrow and small intestine.

Initially isolated from a Norwegian soil sample, Ciclosporin A, the main form of the drug, is a cyclic nonribosomal peptide of 11 amino acids (an undecapeptide) produced by the fungus Tolypocladium inflatum Gams, and contains D-amino acids, which are rarely encountered in nature.

Mode of action

Cyclosporin is thought to bind to the cytosolic protein cyclophilin (immunophilin) of immunocompetent lymphocytes, especially T-lymphocytes.

This complex of cyclosporin and cyclophilin inhibits calcineurin, which under normal circumstances is responsible for activating the transcription of interleukin 2.

It also inhibits lymphokine production and interleukin release and therefore leads to a reduced function of effector T-cells. It does not affect cytostatic activity.

It also has an effect on mitochondria. Cyclosporin A prevents the Mitochondrial permeability transition pore from opening, thus inhibiting cytochrome c release, a potent apoptotic stimulation factor.

However, this is not the primary mode of action for clinical use but rather an important effect for research on apoptosis.