Ciclosporin is an active ingredient from the group of immunosuppressive drugs. It is mainly used to prevent rejection reactions after organ transplants.
What is ciclosporin?
Ciclosporin is the public domain name of an active pharmaceutical ingredient that suppresses the immune system. The drug is made from the Norwegian mushroom species Cylindrocarpon lucidum and Tolypocladium inflatum. Chemically speaking, ciclosporin is a cyclic protein with eleven different amino acid esters.
Cyclosporine was first used in transplant medicine in 1978. This first use was a revolution in this area of medicine, as ciclosporin significantly increased the survival time of the organ recipients. Hartmann Stähelin and Jean-François Borel discovered the drug.
Pharmacological effect
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 meaning for the organism is still unknown. In the case of ciclosporin, they function as an intracellular receptor. The binding to this prolyl-cis-trans-isomerase creates a complex which in turn binds to the 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. It is a gene regulating protein. The activated NFAT normally reaches the cell nucleus and induces the production of cytokines, interleukins and interferons there.
Without inhibiting ciclosporin, numerous immune-stimulating substances are released. Ciclosporin temporarily deactivates this mechanism and thus inhibits the release of immune stimulants and the proliferation of white blood cells. In this way, cyclosporine has an immunosuppressive effect.
Medical application & use
Ciclosporin is used to suppress the immune system. Such immunosuppression is necessary after transplants, for example. After a transplant, the body may recognize the transplanted organ as foreign and attack it. The immune system reacts to the transplant like 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.
Ciclosporin is also used in autoimmune diseases. In an autoimmune reaction, the immune system turns against its own tissue 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. Inflammatory bowel disease is associated with symptoms such as abdominal cramps, diarrhea and severe indigestion.
Glomerulonephritis is also treated with cyclosporine. Glomerulonephritis is a disease of the kidney corpuscles that usually occurs one to two weeks after an upper respiratory tract or ear infection.
Other areas of application for cyclosporine are 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 cyclosporine in the treatment of alopecia areata. Alopecia areata is also known as circular hair loss. It is the most common inflammatory disease with 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 MDR1 transporter is often responsible for resistance to chemotherapy drugs.
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Even in small doses, regular use of cyclosporine can damage the kidneys. Damage to the liver and gastrointestinal tract is also possible. Furthermore, it can lead to growths of the gums and water retention. High blood pressure or hirsutism are also possible side effects. Hirsutism is a male distribution pattern of body hair in women. The affected women have strong hair in the jaw area near their ears, on the upper lip, on the chin, on the chest and on the stomach. The immune system is severely weakened in patients who regularly take high doses of cyclosporine. Transplant patients are usually affected by this immunodeficiency. On the one hand, the immunodeficiency is desired to prevent transplant rejection, on the other hand, it increases the likelihood of cancer by a factor of three to five. In addition, there is an increased risk of infection. Infections that are actually harmless can also take severe courses. In addition, there is an increase in blood lipid levels. Some patients also develop fibroadenomas when taking it. Fibroadenomas are tumorous benign neoplasms in the area of the mammary gland. Strong sunlight should be avoided while taking ciclosporin. UV radiation and light therapy are also contraindicated.
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