Cyclosporine is a drug that belongs to the immunosuppressants. It is obtained from the tubular fungi Cylindrocarpon lucidum and Tolypocladium inflatum. Chemically, it represents a cyclic peptide of eleven amino acids.
What is cyclosporine?
Cyclosporine has a depressant effect on the immune system. It is therefore applied to suppress, for example, the rejection reactions in organ transplants. Cyclosporine is an immunosuppressant with a narrow therapeutic range. The distance between its intended therapeutic effect and its toxic effect is very small. Therefore, blood levels must always be monitored when it is used. Cyclosporine has a depressant effect on the immune system. It is therefore used in diseases characterized by an excessive reaction of the immune system. This includes the group of autoimmune diseases. Cyclosporine is also used to suppress the rejection reactions in organ transplants. It is a cyclic peptide consisting of eleven amino acids. It is found in greater concentrations in the Norwegian tubular mushrooms Cylindrocarpon lucidum and Tolypocladium inflatum. Therefore, it is isolated from these fungi. Today, cyclosporine is produced synthetically for medical use. In its isolated state, it is a white solid that dissolves in alcohol, methanol, chloroform or ether. It is administered orally as a capsule or tablet, or parenterally bypassing the digestive tract (e.g. by injection). Due to its immunosuppressive effect, cyclosporine can also cause several side effects when used. However, the drug has greatly revolutionized medicine with regard to organ transplant rejection. The survival time of patients could be significantly increased. The drug was discovered in the early 1970s by Swiss microbiologists Hartmann Stähelin and Jean-François Borel.
Pharmacological action
The pharmacologic action of cyclosporine is based on its inhibitory action on the enzyme calcineurin. Calcineurin activates the synthesis of interleukins by stimulating the corresponding genes. The enzyme calcineurin is contained in T lymphocytes and from there controls the synthesis of interleukin 2. As a messenger substance, interleukin 2 evokes inflammatory reactions that serve to defend the body against foreign proteins (bacteria, viruses). In autoimmune diseases, however, the body’s own proteins are fought. To stimulate the immune system, calcineurin attaches to the protein NF-AT and dephosphorylates it. In the dephosphorylated state, this protein stimulates the corresponding genes to transcribe interleukins, which are responsible for immune responses. This reaction cascade is inhibited by cyclosporine. For this purpose, cyclosporine attaches itself to certain receptors of the T lymphocytes. There it binds to so-called immunophilins (intracellular binding proteins) and forms a complex with them. This complex in turn attaches to calcineurin. As a result, this enzyme is blocked and can no longer activate the transcription factor NF-AT by dephosphorylation. Further formation of interleukins ceases, thereby attenuating the body’s immune responses.
Medical application and use
Cyclosporine is widely used in autoimmune diseases, psoriasis, inflammatory skin diseases, rheumatic diseases, or organ transplantation. In autoimmune diseases, the immune system directed against its own body, and in organ transplants against the transplanted organs in the form of rejection reactions. Organ transplanted patients in particular benefit from the use of this drug. For example, since its use, the survival time of those affected has increased dramatically. Severe autoimmunological diseases such as ulcerative colitis or glomerulonephritis can also be treated well. In ulcerative colitis, the intestine is attacked by the patient’s own immune system. This disease is characterized by severe intestinal inflammation that can eventually destroy the intestine. Glomerulonephritis represents an abacterial inflammation of the glomeruli of the kidneys. If left untreated, it can lead to severe renal insufficiency. Psoriasis can also be treated well with cyclosporine. For inflammation of the conjunctiva and cornea, cyclosporine is used by topical application.This involves applying medication containing cyclosporine to the affected areas. Typically, cyclosporine is also used for neurodermatitis. Neurodermatitis is an inflammatory, highly itchy skin disease caused by allergic reactions. Finally, an important area of application is rheumatoid arthritis. Rheumatoid arthritis is an autoimmune disease in which the immune system attacks the body’s own joints. The treatment spectrum of cyclosporine also includes severe inflammatory eye diseases that can lead to blindness. Treatment with cyclosporine is life-saving in many cases (organ transplantation, severe organ-destroying autoimmune diseases). It also improves the quality of life of many patients with chronic inflammatory diseases.
Risks and side effects
Unfortunately, cyclosporine cannot be used without restriction because it can cause many side effects. The side effects and contraindications largely result from the weakening of the immune system. For example, patients with infections should not be treated with cyclosporine. Immunosuppression could make the infection worse. Pregnant women and nursing mothers should also not be treated with cyclosporine, as the drug could have a harmful effect on the child. The simultaneous use of phototherapy for psoriasis and treatment with cyclosporine increases the risk of skin cancer. Therapy with cyclosporine is also counterproductive in cases of kidney damage, as the kidneys may be further damaged. Overall, susceptibility to infection increases with the use of cyclosporine, which is due to the reduced immune response. Gastrointestinal disturbances may initially occur, leading to diarrhea, nausea, and vomiting. Furthermore, the development of edema is possible. There may also be an increase in body hair. The list of possible side effects is very long. However, these do not have to occur. However, digestive disorders, headaches, gingivitis or increased blood pressure occur more frequently. Therefore, blood tests and blood pressure measurements should be performed regularly during treatment with cyclosporine.
