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A comparative study on immunosuppressive effects of cyclosporin A and FK 506 on peripheral blood lymphocytes in dogs
Authors:Kyoichi Takaori  Yoshinori Nio  Kazutomo Inoue  Thein Tun  Manaba Fukumoto  Tohru Hashida  Masato Yasuhara  Ryohei Hori  Takayoshi Tobe
Institution:(1) The First Department of Surgery, Kyoto University Faculty of Medicine, 606 Kyoto, Japan;(2) The First Department of Pathology, Kyoto University Faculty of Medicine, 606 Kyoto, Japan;(3) The Department of Pharmacy, Kyoto University Faculty of Medicine, 606 Kyoto, Japan
Abstract:Immunosuppressive effects of cyclosporin A (CsA) and FK 506 (FK) on peripheral blood lymphocytes were studied in dogs in respect to mixed lymphocyte reaction, proliferative responses to recombinant interleukin-2 (rIL-2), phytohemagglutinin (PHA) and concanavalin-A (Con-A); phenotypes of OKIa1, CD3, CD8 and surface IgM; cytotoxic activity against xenogeneic tumor cells. CsA (2.0 or 5.0 mg/kg, intravenously) or FK (0.16 mg/kg, intramuscularly) was given to mongrel dogs every morning for serial 21 days. The blood concentrations of CsA, measured as trough levels by fluorescence polarization method, ranged from 37 to 350 ng/ml in dogs administered at 2.0 mg/kg and from 170 to 894 ng/ml in dogs administered at 5.0 mg/kg during treatment, respectively. In dogs treated with FK at a dose of 0.16 mg/kg, the drug concentrations in the plasma during treatment ranged from 0.16 to 1.8 ng/ml. Mixed lymphocyte reaction and proliferative responses to rIL-2, PHA and Con-A, which were declined by CsA, were not affected by FK. In contrast, the proportion of OKIa1+ cells was not affected by CsA, whereas FK decreased the proportion of OKIa1+ cells progressively during the course of treatment. Cytotoxic activity was suppressed by both CsA and FK. These results possibly indicate that CsA and FK exert their immunosuppressive effects via different mechanisms.
Keywords:canine immunity  cyclosporin A  FK 506  immunosuppression  transplantation
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