CsA

Cyclosporin A (CsA) is a cyclic peptide immunosuppressant produced by the fungus Tolypocladium inflatum. It is used to prevent organ rejection in transplant recipients and, in select cases, to treat certain autoimmune diseases when other therapies are inadequate.

CsA exerts its immunosuppressive effect by binding to the intracellular protein cyclophilin. The CsA–cyclophilin complex inhibits calcineurin, a calcium–calmodulin–dependent phosphatase, preventing the activation of NFAT transcription factors. This reduces transcription of interleukin-2 and other cytokines, thereby suppressing T‑cell activation and proliferation.

Clinically, CsA is a cornerstone of modern solid organ transplantation regimens, used to reduce acute rejection and improve graft survival, usually in combination with corticosteroids and other agents. It is also employed in certain autoimmune diseases and inflammatory conditions under specialist supervision.

Pharmacologically, CsA is highly lipophilic and extensively protein bound. It is administered orally or intravenously, with variable oral bioavailability. It is principally metabolized by hepatic cytochrome P450 3A4 and excreted in bile, with renal clearance minimal. Plasma levels are monitored to guide dosing.

Because CsA interacts with many drugs, patients require careful monitoring. Inhibitors of CYP3A4 (for example ketoconazole, itraconazole) raise CsA levels and risk toxicity, while inducers (rifampin, phenobarbital) lower levels. Grapefruit juice can elevate levels.

Common adverse effects include nephrotoxicity and hypertension, which are dose dependent, as well as tremor, headache, hepatotoxicity, hyperlipidemia, gingival hyperplasia, hirsutism, and an increased susceptibility to infections and malignancies due to immunosuppression. Long-term use requires regular laboratory monitoring and assessment for organ function.

Cyclosporin A was isolated in the 1970s from Tolypocladium inflatum by pharmaceutical researchers and introduced for clinical use in the 1980s. Its introduction transformed transplantation by enabling more effective suppression of immune rejection.