Cyclosporine: immunology, toxicity and pharmacology in experimental animals.
Cyclosporine (CsA) is the first of a new order of pharmacological immune suppressants and represents a significant advance in the clinical control of graft rejection. In laboratory animals, its capacity to prolong allograft survival has been well documented, including reports of indefinite donor-specific immunological tolerance after shortterm CsA treatment. There is also evidence that CsA can inhibit the onset or progress of a variety of experimental autoimmune diseases. Underlying these properties of the drug is its capacity to selectively interfere with T helper cell activation and lymphokine production, although some direct effects on B cells have also been reported. In addition, sparing of suppressor cells may in part explain the mode of action of CsA which, at the molecular level, is not understood. CsA-induced nephrotoxicity in the rat has been extensively studied and is characterized by reversible proximal tubular cell damage. This problem may be aggravated by concomitant administration of other potentially nephrotoxic drugs, such as gentamicin, or by therapeutic agents which interfere with the metabolism of CsA. CsA is metabolized in the liver and excreted in the bile. Although the pathway of hepatic metabolism of CsA has not been precisely elucidated, animal studies suggest that agents capable of inducing metabolism of the drug CsA could be used to alleviate its nephrotoxic properties.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001327:Autoimmune Diseases / Q000188:drug therapy; D002273:Carcinogens; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003524:Cyclosporins / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D004064:Digestive System / Q000187:drug effects; D006084:Graft Rejection / Q000187:drug effects; D006087:Graft vs Host Reaction / Q000187:drug effects; D006413:Hematopoietic System / Q000187:drug effects; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007166:Immunosuppressive Agents; D007668:Kidney / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008208:Lymphatic System / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000096:biosynthesis; D009153:Mutagens; D012867:Skin / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects
D002273:Carcinogens; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D008222:Lymphokines; D009153:Mutagens