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, Volume 15, Issue 3–4, pp 306–327 | Cite as

Cyclosporine: Immunology, toxicity and pharmacology in experimental animals

  • A. W. Thomson
  • P. H. Whiting
  • J. G. Simpson
Immunosuppression and Inflammation Review

Abstract

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.

Keywords

Cyclosporine Gentamicin Graft Rejection Suppressor Cell Concomitant Administration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag 1984

Authors and Affiliations

  • A. W. Thomson
    • 1
  • P. H. Whiting
    • 1
  • J. G. Simpson
    • 1
  1. 1.Departments of Pathology and Chemical PathologyUniversity Medical BuildingsAberdeenScotland, UK

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