Ciclosporin is an active substance from the group of immunosuppressive drugs. It is predominantly used to prevent rejection after organ transplantation.
What is ciclosporin?
Ciclosporin is an active substance from the group of immunosuppressive drugs. It is used primarily to prevent rejection after organ transplantation. Ciclosporin is the common name of a drug substance that suppresses the immune response. The drug is produced from the Norwegian fungal species Cylindrocarpon lucidum and Tolypocladium inflatum. Chemically, ciclosporin is a cyclic protein with eleven different amino acid esters. Ciclosporin was first used in transplantation medicine in 1978. This initial use was a revolution in this field of medicine, as ciclosporin significantly increased the survival time of organ recipients. The discoverers of the drug were Hartmann Stähelin and Jean-François Borel.
Pharmacologic action
Ciclosporin is a so-called cyclic protein. It binds to cyclophilin A. This is an immunophilin. Immunophilins are proteins that are found in the body’s cells. Their exact significance for the organism is still unknown. In the case of ciclosporin, they function as intracellular receptors. Binding to this prolyl cis-trans isomerase creates a complex, which in turn binds to calcineurin. Calcineurin is a phosphatase that is calcium and calmodulin dependent. The complex of cyclophilin A and ciclosporin prevents the activation of the nuclear factor acticatin T-Cell (NFAT) in calcineurin. This is a gene-regulating protein. Normally, activated NFAT enters the nucleus and induces the production of cytokines, interleukins and interferons. Without inhibition of ciclosporin, numerous immunostimulatory substances are released. Ciclosporin temporarily deactivates this mechanism and thus inhibits the release of immunostimulants and the proliferation of white blood cells. In this way, ciclosporin has an immunosuppressive effect.
Medical use and application
Ciclosporin is used to suppress the immune system. Such immunosuppression is necessary after transplantation, for example. After transplants, the body may recognize the transplanted organ as foreign and attack it. In this case, the immune system reacts to the transplant as it would to a pathogen. Such rejection reactions can occur days, months or even years after the operation. Immunosuppressants such as ciclosporin are used to prevent these reactions. However, ciclosporin is also used for autoimmune diseases. In an autoimmune reaction, the immune system turns against its own tissues or organs for reasons that are often still unknown. Ulcerative colitis and Crohn’s disease are among the autoimmune diseases that are treated with ciclosporin. The chronic inflammatory bowel diseases are accompanied by symptoms such as abdominal cramps, diarrhea and severe digestive disorders. Glomerulonephritis is also treated with ciclosporin. Glomerulonephritis is a disease of the renal corpuscles that usually occurs one to two weeks after an upper respiratory or ear infection. Other indications for ciclosporin include severe or even therapy-resistant skin diseases such as psoriasis or atopic dermatitis (neurodermatitis) and chronic inflammation of the conjunctiva or cornea. In combination with the drug methylprednisolone, good results are achieved with ciclosporin in the treatment of alopecia areata. Alopecia areata is also known as circular hair loss. It is the most common inflammatory condition involving hair loss. Ciclosporin is also used in cancer therapy. Together with the drug verapamil, it prevents chemotherapeutic agents from being transported out of the target cells by the multidrug resistance protein 1. The transporter MDR1 is often responsible for resistance to chemotherapeutic agents.
Risks and side effects
Even at lower doses, regular use of ciclosporin can damage the kidneys. Damage to the liver and gastrointestinal tract is also possible. Furthermore, growths of the gums and water retention may occur. High blood pressure or hirsutism are also possible side effects. Hirsutism is a male pattern of body hair distribution in women.In affected women, for example, strong hairs are found in the jaw area near the ear, on the upper lip, on the chin, on the chest and on the abdomen. In patients who regularly take high doses of ciclosporin, the immune system is severely weakened. As a rule, transplant patients are affected by this immune deficiency. On the one hand, the immunodeficiency is desired for the prevention of transplant rejections; on the other hand, it increases the probability of cancer by a factor of three to five. In addition, there is an increased risk of infection. Even infections that are actually harmless can take a severe course. In addition, there is an increase in blood lipid levels. Some patients also develop fibroadenomas when taking the drug. Fibroadenomas are tumorous benign neoplasms in the area of the mammary gland. Strong sun exposure should be avoided while taking ciclosporin. UV irradiation and light therapy are also contraindicated.