Yamamoto K, Mori A, Nakahama T, Ito M, Okudaira H, Miyamoto T
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Immunology. 1990 Feb;69(2):222-7.
A newly developed immunosuppressive drug, FK506 (Fujisawa, Japan) is known to inhibit T-cell immunity. We have evaluated the action of this compound in MRL/lpr mice which develop a severe autoimmune disease. Eight-week-old female MRL/lpr of mice were treated subcutaneously with 2 mg/kg (high dose), 0.8 mg/kg (medium dose), 0.2 mg/kg (low dose) or solvent only (control) six times per week. Survival times of the mice were prolonged in the medium and the high dose treatment groups. The lymph node swelling was dramatically prevented with the high dose treatment. The increasing footpad swelling seemed to be also suppressed with the treatment. FACS analyses of the spleen cells revealed that FK506 reduced the percentage of double negative T cells (Thy-1.2+, Lyt-2-, L3T4-). Serological studies showed that anti-ssDNA and anti-dsDNA activities were significantly reduced by the high dose treatment, which is different from recent findings with Cyclosporine A. The high dose treatment also suppressed the total amount of IgG, even though the IgG concentration was rather increased by the medium dose treatment. Decreased proteinuria as well as pathological evaluations of the kidneys and lungs indicated that there were marked ameliorations in these organs with the treatment. These results suggest that FK506 could be potentially used for the treatment of autoimmune diseases.
一种新开发的免疫抑制药物FK506（日本藤泽公司生产）已知可抑制T细胞免疫。我们评估了该化合物在患有严重自身免疫性疾病的MRL/lpr小鼠中的作用。8周龄雌性MRL/lpr小鼠每周皮下注射2 mg/kg（高剂量）、0.8 mg/kg（中剂量）、0.2 mg/kg（低剂量）或仅注射溶剂（对照）6次。中剂量和高剂量治疗组小鼠的存活时间延长。高剂量治疗显著预防了淋巴结肿大。治疗似乎也抑制了足垫肿胀的加剧。对脾细胞的流式细胞术分析显示，FK506降低了双阴性T细胞（Thy-1.2+、Lyt-2-、L3T4-）的百分比。血清学研究表明，高剂量治疗可显著降低抗单链DNA和抗双链DNA活性，这与环孢素A的近期研究结果不同。高剂量治疗还抑制了IgG的总量，尽管中剂量治疗使IgG浓度有所升高。蛋白尿减少以及对肾脏和肺部的病理学评估表明，治疗后这些器官有明显改善。这些结果表明，FK506可能潜在地用于治疗自身免疫性疾病。
