STUDIES ON THE EFFECTS OF CYCLOSPORIN-A UPON RENAL-ALLOGRAFT REJECTION IN THE DOG

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 88  (1) , 168-173
Abstract
Dose and time response studies of the new immunosuppressive agent, cyclosporin A, were performed in a dog renal allograft model. Rejection of a renal allograft only occurred in 1 of 6 dogs receiving 20 mg/kg per day continuously, but in 10 of 11 dogs receiving 10 mg/kg per day. Doses of 10 or 20 mg/kg per day given for 2 or 3 wk delayed rejection, but rejection occurred in all animals when the drug was stopped. This suggests that the drug does not produce clonal deletion of the lymphocytes engaged in the immune reaction against the graft, but merely their suppression. The histological picture of rejection was markedly improved by therapeutic doses of cyclosporin A. No consistent histological or biochemical evidence for hepatoxicity or nephrotoxicity was found even in the higher doses tested. One fatal and 4 non-fatal infectious complications were seen in 29 dogs receiving doses of 5 mg/kg per day or higher.