Cyclosporine: a new immunosuppressive agent for organ transplantation.
ABSTRACT Cyclosporine, a cyclic endecapeptide of fungal origin, has recently been released for use in clinical transplantation. Trials in kidney, heart, liver and bone marrow recipients were encouraging: 1-year graft survival rates were 70% to 80% for kidney and heart recipients, and 60% to 65% for liver allograft recipients. Cyclosporine is also effective in treating bone marrow recipients with acute graft-versus-host disease. The drug selectively inhibits T-helper cell production of growth factors essential for B cell and cytotoxic T-cell differentiation and proliferation, while allowing expansion of suppressor T-cell populations. Drug absorption varies greatly, necessitating monitoring of drug level and individualization of therapy. Nephrotoxicity is the most frequent side effect of cyclosporine. An increased incidence of B-cell lymphomas seen when cyclosporine was used in conjunction with cytotoxic agents or anti-lymphocyte globulin has very rarely been observed when concomitant immunosuppression has been limited to low-dose corticosteroids. Lower initial doses of cyclosporine, followed by more rapid tapering may reduce the incidence of nephrotoxicity without compromising improved graft outcome.
- SourceAvailable from: Carolyn Geczy[show abstract] [hide abstract]
ABSTRACT: Cyclosporin A (Cs A) exerted a dose-related inhibitory effect on antigen (ovalbumin, OVA) and phytohaemagglutinin (PHA)-induced transformation of guinea-pig lymph node cells (LNC). Whereas 0.05 micrograms/ml was sufficient to depress these responses markedly, it required 100-fold this concentration of Cs A to inhibit the production of lymphocyte activating factor (LAF) by lipopolysaccharide (LPS) stimulated peritoneal macrophages. Addition of Cs A together with insoluble concanavalin A (iCon A) to LNC cultures resulted in suppressed lymphokine production, as assessed by measurement of migration inhibition factor (MIF), the generation of macrophage procoagulant activity (MPCA) and the release of lymphocyte-derived-macrophage chemotactic factor (LDCF). Cs A also inhibited MIF and procoagulant production by sensitized peritoneal exudate cells in response to antigen, at the same concentrations which blocked lymphocyte transformation. In contrast, Cs A had no direct effect on the migration of peritoneal cells from capillary tubes, or on the responses of macrophages to preformed MIF, the lymphokine inducing MPCA or LDCF. Overnight incubation of macrophages with Cs A did, however, result in mild inhibition of their basal level of procoagulant activity.Immunology 03/1983; 48(2):291-9. · 3.71 Impact Factor
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ABSTRACT: Cyclosporin A (Cy A, 25 or 50 mg.kg-1/48 hr) administered during the course of the response, markedly suppressed graft-versus-host (GVH) reactivity in the rat, as assessed by the 7-day popliteal lymph node weight assay. Serum biochemical studies revealed small, but statistically significant increases in serum urea levels at both doses of Cy A and, at 50 mg.kg-1/48 hr, reduction in total serum protein, alkaline phosphatase, serum transaminase, and iron. In an additional experiment, Cy A (50 mg.kg-1/48 hr) was administered to rats over 4 weeks. Serum biochemical and hematological investigations were conducted at weekly intervals and at 28 days tissue (liver, kidney, spleen, lymph nodes, and small intestine) was taken for histological and ultrastructural examination. Glomerular function, monitored by creatinine and urea clearance was unaffected by Cy A treatment, but serum urea and creatinine levels were elevated. Hepatic function was not affected and hematological, histological, and ultrastructural observations, apart from evidence of hepatic fatty change, did not differ from those in vehicle-treated controls.Transplantation 03/1981; 31(2):121-4. · 3.78 Impact Factor
- Biological effects of cyclosporin A: a new antilymphocyte agent. 468-75..