“Vasile Alecsandri” High School, Galati, Romania
In 1971 a new era began in immunopharmacology, with the discovery of the first immunosuppressive drug allowing immunoregulation of T cells with minimum toxicity- Cyclosphorin. The new drug was isolated from the fungus Tolypocladium inflatum and was first investigated as an anti-fungal antibiotic but its spectrum was too narrow to be of any clinical use. J. F. Borel discovered its immunosuppressive activity in 1976.This led to further investigations into its properties involving further immunological tests and investigations into its structure and synthesis. Cyclosporin has unwanted side effects, notably nephrotoxicity. Animal testing showed cyclosporin to be sufficiently non-toxic to begin clinical trials. These initially failed due to poor absorption of the drug. Once this had been overcome, results were encouraging enough for cyclosporin to be licensed for use in clinical practice. There is some controversy between Borel and other workers over priority in the discovery of cyclosporin and its pre-clinical development, which is examined in this review. Cyclosporin changed the face of transplantation. It decreased morbidity and enabled the routine transplantation of organs that until then had only been done experimentally.
What exactly is cyclosporin and what are its uses?
Cyclosporin molecule
Today organ and bone marrow transplants are routinely performed. Cyclosporin is still used to treat the rejection reactions that occur when a foreign organ is attacked by the body’s immune system. Cyclosporin is a fungal peptide, isolated from Tolypocladium inflatum Gams. It was the first immunosuppressant that acted selectively to suppress T-cell immunity.
Cyclosporin is at present approved for use in organ transplantation to prevent graft rejection in kidney, liver, heart, lung and combined heart-lung transplants. It is used to prevent rejection following bone marrow transplantation and in the prophylaxis of host-versus-graft disease. It is also used in the treatment of psoriasis, atopic dermatitis, rheumatoid arthritis and nephrotic syndrome.
Why was the discovery of cyclosporin so important?
Discovery of immunosuppression by cyclosporin in 1976 is attributed to J. F. Borel. In 1983 cyclosporin was approved for clinical use to prevent graft rejection in transplantation. Most of the surgical problems of allograft transplantation had already been solved by this time.
Cyclosporin was the strongest immunosuppressor to be discovered so far, it also overcame many of the risk factors associated with azathioprine and is relatively non-toxic to bone marrow. With the introduction of cyclosporin patient morbidity fell. It became possible to transplant organs with a one year success of 20% higher than previously , and to transplant organs successfully which previously had only been done in experimentation: the heart, the liver, the lung and combined heart lung transplants .
As well as transplantation, cyclosporin has been used in most autoimmune diseases. In the 1980’s experimental treatment with cyclosporin of insulin-dependent diabetes mellitus, inflammatory bowel disease, chronic asthma, atopic dermatitis, aplastic anaemia and psoriasis supported evidence of their T cell mediated nature .
What exactly is cyclosporin and what are its uses?
Cyclosporin molecule
Today organ and bone marrow transplants are routinely performed. Cyclosporin is still used to treat the rejection reactions that occur when a foreign organ is attacked by the body’s immune system. Cyclosporin is a fungal peptide, isolated from Tolypocladium inflatum Gams. It was the first immunosuppressant that acted selectively to suppress T-cell immunity.
Cyclosporin is at present approved for use in organ transplantation to prevent graft rejection in kidney, liver, heart, lung and combined heart-lung transplants. It is used to prevent rejection following bone marrow transplantation and in the prophylaxis of host-versus-graft disease. It is also used in the treatment of psoriasis, atopic dermatitis, rheumatoid arthritis and nephrotic syndrome.
Why was the discovery of cyclosporin so important?
Discovery of immunosuppression by cyclosporin in 1976 is attributed to J. F. Borel. In 1983 cyclosporin was approved for clinical use to prevent graft rejection in transplantation. Most of the surgical problems of allograft transplantation had already been solved by this time.
Cyclosporin was the strongest immunosuppressor to be discovered so far, it also overcame many of the risk factors associated with azathioprine and is relatively non-toxic to bone marrow. With the introduction of cyclosporin patient morbidity fell. It became possible to transplant organs with a one year success of 20% higher than previously , and to transplant organs successfully which previously had only been done in experimentation: the heart, the liver, the lung and combined heart lung transplants .
As well as transplantation, cyclosporin has been used in most autoimmune diseases. In the 1980’s experimental treatment with cyclosporin of insulin-dependent diabetes mellitus, inflammatory bowel disease, chronic asthma, atopic dermatitis, aplastic anaemia and psoriasis supported evidence of their T cell mediated nature .
Bibliography :
en.wikipedia.org/wiki/Cyclosporine (image also)
http://www.erj.ersjournals.com/cgi/content/full/23/1/159
http://www.bjhm.co.uk/cgi-bin/go.pl/library/article.cgi?uid=1118;article=hm_60_5_364_369
http://www.sandimmune.ch/texte/experientia.pdf
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