Cyclosporine

Cyclosporine, also spelled ciclosporin or cyclosporin A, originated from a soil fungus isolated in the 1970s. Its cyclic ring contains 11 amino acids, including unusual residues, producing a fat-soluble structure unlike a typical linear peptide. Systemic products include Sandimmune, Neoral microemulsion and Gengraf; Restasis is an ophthalmic emulsion.

Selective T-cell suppression, rather than broad bone-marrow elimination, transformed organ transplantation after US approval in 1983 during the transformation of transplantation in the 1980s. Improved graft survival helped heart, liver and other transplants become routine clinical procedures. Cyclosporine remains a reference calcineurin inhibitor.

The products include oral, intravenous and ophthalmic forms; route and formulation are not interchangeable.

Inside T cells, cyclosporine binds cyclophilin. The complex inhibits calcineurin, preventing NFAT activation and subsequent interleukin-2 and related signals needed for T-cell expansion. This suppresses rejection responses or pathological immune activation.

The landmark Canadian multicenter transplant trial found better one-year kidney-graft survival than the older azathioprine-based regimen. The same immunological pathway supports selected autoimmune uses and local reduction of chronic dry-eye inflammation.

Systemic use includes prevention of kidney, liver and heart transplant rejection and severe rheumatoid arthritis or plaque psoriasis unresponsive to other treatment. Restasis increases tear production in inflammatory chronic dry eye. Oral formulations are not freely interchangeable and require clinical/blood-level monitoring.

Systemic effects include hypertension, impaired renal function/rising creatinine, tremor, excess hair growth and gingival overgrowth. Boxed warnings address kidney toxicity and serious infections/malignancies associated with immunosuppression, particularly lymphoma and skin cancer.

Numerous drug interactions and variable exposure require blood-level monitoring. Restasis acts locally and mainly causes ocular burning or stinging; it does not carry the same systemic warning profile. Systemic safety conclusions should not be transferred automatically to the eye formulation or vice versa.