Takaori K, Nio Y, Inoue K, Tun T, Fukumoto M, Hashida T, Yasuhara M, Hori R, Tobe T
First Department of Surgery, Kyoto University Faculty of Medicine, Japan.
Biotherapy. 1992;4(2):129-37. doi: 10.1007/BF02171757.
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.
研究了环孢素A（CsA）和FK 506（FK）对犬外周血淋巴细胞的免疫抑制作用，涉及混合淋巴细胞反应、对重组白细胞介素-2（rIL-2）、植物血凝素（PHA）和刀豆蛋白A（Con-A）的增殖反应；OKIa1、CD3、CD8和表面IgM的表型；对异种肿瘤细胞的细胞毒活性。杂种犬每天早晨静脉注射CsA（2.0或5.0mg/kg）或肌肉注射FK（0.16mg/kg），连续21天。用荧光偏振法测定谷浓度时，治疗期间给予2.0mg/kg CsA的犬，其血药浓度范围为37至350ng/ml，给予5.0mg/kg CsA的犬，血药浓度范围为170至894ng/ml。给予0.16mg/kg FK治疗的犬，治疗期间血浆中药物浓度范围为0.16至1.8ng/ml。CsA可降低混合淋巴细胞反应以及对rIL-2、PHA和Con-A的增殖反应，而FK对此无影响。相反，CsA不影响OKIa1+细胞比例，而FK在治疗过程中可使OKIa1+细胞比例逐渐降低。CsA和FK均可抑制细胞毒活性。这些结果可能表明CsA和FK通过不同机制发挥免疫抑制作用。
