Cyclosporine autoimmune diseases

Immunosuppression induced by sirolimus (36) appears to be mediated by a mechanism distincdy different from that of either cyclosporin or FK-506. Sirolimus markedly suppresses IL-2 or IL-4-driven T-ceU proliferation. The preclinical studies suggest that sirolimus is a potent immunosuppressive agent in transplantation and autoimmune disease models. The clinical potential of this agent depends on its toxicity profile (80). 

The first human kidney and bone marrow transplants using cyclosporine were reported in 1978. Oral or intravenous cyclosporine is an immunosuppressant for transplantation of these and other organs and investigations are underway for its possible use in a variety of autoimmune diseases including rheumatoid arthritis, severe psoriasis, and Crohn s disease. Dose-dependent nephrotoxicity (261—264) remains the primary limitation of the dmg and necessitates close monitoring of patients, including measurement of dmg levels in blood. Cyclosporine research has been reviewed (265—274). 

R. Schindler, ed.. Cyclosporin in Autoimmune Diseases, Springer-Vedag, Berlin, 1985. 

Calcineurin is involved in cardiac hypertrophy and in cognitive and behavioral defects in the brain. Inhibitors of calcineurin such as cyclosporine A and FK 506 are used clinically in transplant rejection and autoimmune diseases. 

Cyclosporin-A In 1972, the immunosuppressive effect of cyclosporin-A, an antibiotic secreted by some fungi, was discovered. Other antibiotics also have immunosuppressive effects. They interfere with proliferation of T-helper cells by preventing the entry of a transcription factor into the nucleus. This prevents transcription of the genes involved in the proliferative process. Their use is restricted to patients after transplantation, since there are serious side-effects, for example, toxic effects on the mbules of the kidney. This precludes their use for treatment of non-life-threatening autoimmune diseases. 

Cyclosporine (Sandimmune) is a potent inhibitor of antibody- and cell-mediated immune responses and is the immunosuppressant of choice for the prevention of transplant rejection. It also has application in the treatment of autoimmune diseases. 

Cyclosporine appears to have promise in the treatment of autoimmune diseases. It has a beneficial effect on the course of rheumatoid arthritis, uveitis, insulin-dependent diabetes, systemic lupus erythematosus, and psoriatic arthropathies in some patients. Toxicity is more of a problem in these conditions than during use in transplantation, since higher doses of cyclosporine are often required to suppress autoimmune disorders. 

The drugs like azathioprine and cyclosporine A are used chiefly to prevent transplant rejection and in the treatment of autoimmune diseases. They are used to prevent graft rejection after kidney, liver, lung, pancreas transplant or bone marrow transplantation. 

These are the agents used to suppress the immunity. The drugs like azathioprine and cyclosporin A are used chiefly to prevent rejection in organ transplantation. They are also used for treatment of autoimmune disease. 

Autoreactive tissue disorders (autoimmune diseases)2 Prednisone, cyclophosphamide, methotrexate, interferon-a and -3, azathioprine, cyclosporine, infliximab, etanercept, adalimumab Often good, variable... 

Cyclosporine is used to a somewhat lesser extent in treating autoimmune diseases, but it may be helpful in conditions such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, and glomerulonephri-tiS.i5,32,63 as discussed in Chapter 32, cyclosporine has also been used in the early stages of type 1 diabetes mellitus to help control immune-mediated destruction of pancreatic beta cells, thus decreasing the severity of this disease in some patients.9... 

Cyclosporin A, which has been used as an immunosuppressant with fungicidal and anti-inflammatory properties in bone marrow and organ transplants and in autoimmune diseases since 1983, was isolated from a fungal culture (Tolypocladium)144). 

Cyclosporine is an important drug in preventing rejection after kidney, hver, heart and other organ transplantation (Haberal et al., 2004). Cyclosporine usually is combined with other immunosuppressives especially glucocorticoids and either azathioprine or mycophenolate mofedl and sirolimus (Krensky et al., 2005). In renal alio transplants it has improved graft acceptance in most clinics to 95 percent. In addition to its use in transplantation cyclosporine is used for the treatment of a number of autoimmune diseases. In autoimmune diseases, as might be anticipated, cyclosporine is most effective in those which are T cell mediated. These include several forms of psoriasis, rheumatoid arthritis refractive to all other therapy, uveitis, nephrotic syndrome and type I diabetes mellitus. 

Feutren G, Mihatsch MJ. Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. International Kidney Biopsy Registry of Cyclosporine in Autoimmune Diseases. N Engl J Med 1992 326(25) 1654-60. 

The situation where the CSA impact on native kidneys is most evident is the treatment of autoimmune diseases. In these patients rejection is not an issue, and the native kidneys are usually healthy and not submitted to other potential insults, making it easier to establish a direct cause-effect correlation. In fact, Feutren and Mihatsch, on behalf of the International Kidney Biopsy Registry of Cyclosporine in Autoimmune Diseases, found interstitial fibrosis and tubular... 

Langford CA, Klippel JH, Balow JE, James SP, Sneller MC. Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease. Part 1 rheumatologicand renal diseases. Ann Intern Med 1998 128 1021-1028. 

Svenson K, Bohman SO, Hallgren R. Renal interstitial fibrosis and vascular changes. Occurrence in patients with autoimmune diseases treated with cyclosporine. Arch Intern Med 1986 146 2007-2010. 

Nakamura T, Nozu K, lijima K, Yoshikawa N, Moriya Y, Yamamori M, Kako A, Matsuo M, Sakurai A, Okamura N, Ishikawa T, Oku-mura K, Sakaeda T. Association of cumulative cyclosporine dose with its irreversible nephrotoxicity in Japanese patients with pediatric-onset autoimmune diseases. Biol Pharm Bull 2007 30 2371-2375. 

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