THE ROLE OF CYCLOSPORINE IN IMMUNOMODULATION

摘要

Cyclosporine is a potent immunosuppressive agent with treatment applications in both human and veterinary medicine. It is a cyclic polypeptide derived from the soil fungus Tolypocladium inflatum. Cyclosporine was discovered in the Sandoz laboratory byBorel in Switzerland in the 1970s, who demonstrated in vitro inhibition of human immune reactions as well as prolonged survival of skin grafts.1 This data was presented in 1976 at the British Society of Immunology, paving the pathway towards utilizationof its immunosuppressive abilities with organ transplantation in human medicine.1'2 Cyclosporine was first described in human medicine by Calne in 1978 with published data documenting prevention of organ rejection in those receiving renal allografts.2 Once these results were shown to be repeatable, cyclosporine became and still remains a cornerstone of immunosuppression in human transplant medicine. Cyclosporine was approved by the U.S. Food and Drug Administration in 1983 for the treatment and prevention of transplant rejection in human medicine. Novartis Animal Health received FDA approval in 2003 for oral cyclosporine capsules marketed as Atopica~R for the treatment of atopic dermatitis in dogs. Cyclosporine is currently being applied to a spectrumof inflammatory and immune-mediated diseases in dogs, including but not limited to atopic dermatitis, keratoconjunctivitis sicca, autoimmune skin disorders, perianal fistula, inflammatory bowel disease, granulomatous meningoencephalitis, and immune-mediated blood disorders such as immune-mediate hemolytic anemia and immune-mediated thrombocytopenia. Cyclosporine has also been used in canine organ transplantation.