Cyclosporine, Ciclosporin (INN), or cyclosporin (former BAN), is an immunosuppressant drug. It is widely used post-allogenic 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, lung, pancreas, bone marrow and small intestine. Cyclosporine is a cyclic nonribosomal peptide of 11 amino acids produced by the fungus Hypocladium inflatum gams, initially isolated from a Norwegian soil sample.

Naming
Although the international noproprietary name is now ciclosporin, it is still referred to as cyclosporine in most scientific journals and medical publications.

Commercialization
The drug is sold by Novartis under the brand names Sandimmune® and Neoral®. Generic cyclosporine drugs have been produced by companies such as Sangstat, Abbott Laboratories and Gengraf. Since 2002 a topical emulsion of cyclosporine for treating keratoconjunctivitis sicca has been marketed under the trade name Restasis®. Annual sales of cyclosporine are around $1 billion.

Uses
The immuno-suppressive effect of Cyclosporine was discovered on January 31, 1972, by the company of Sandoz (nowadays Novartis) in Basle, Switzerland, in a screening test on immune-suppression designed and implemented by Dr. Hartmann F. Stähelin, M.D.. Cyclosporine was subsequently approved for use in 1983.

Apart from in transplant medicine, cyclosporine is also used in psoriasis and infrequently in rheumatoid arthritis and related diseases, although it is only used in severe cases. It has been investigated for use in many other autoimmune disorders. It is often taken in conjunction with corticosteroids. More recently, cyclosporine has begun to be used to help treat patients suffering from ulcerative colitis with positive results.

Mode of action
Cyclosporine is thought to bind to the cytosolic protein cyclophilin (immunophilin) of immunocompetent lymphocytes, especially T-lymphocytes. This complex of cyclosporin and cyclophylin 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.

Side-effects and interactions
Treatment has a number of potentially serious side effects and has adverse interactions with a wide variety of other drugs and other materials including grapefruit, although there have been studies to improve the blood level of cyclosporine with grapefruit juice. Side effects can include gum hyperplasia, convulsions, peptic ulcers, pancreatitis, fever, vomiting, diarrhea, confusion, breathing difficulties, numbness and tingling, pruritus, high blood pressure, kidney and liver disfunction, potassium retention and possibly hyperkalemia, hepatotoxicity, nephrotoxicity, and obviously an increased vulnerability to opportunistic fungal and viral infections.