Inamura N, Hashimoto M, Nakahara K, Nakajima Y, Nishio M, Aoki H, Yamaguchi I, Kohsaka M
Exploratory Research Laboratory, Fujisawa Pharmaceutical Co., Ltd, Ibaraki, Japan.
Int J Immunopharmacol. 1988;10(8):991-5. doi: 10.1016/0192-0561(88)90046-x.
We investigated the effect of a new immunosuppressant, FK506, on the development of experimental allergic encephalomyelitis (EAE) in rats. EAE developed in 100% of rats immunized with myelin basic protein (MBP) in complete Freund's adjuvant. FK506 in doses of 1.0 mg/kg/day or more prevented the clinical signs of EAE for at least 50 days, when administered intramuscularly 5 days a week for 2 weeks starting on the day of immunization (days 0-4 and days 7-11), and a similar result was obtained, when the compound was given for 5 days (days 0-4). FK506, however, showed a significant but weak effectiveness when started from 7 days after immunization. Delayed-type hypersensitivity (DTH) to MBP developed before EAE, and anti-MBP antibody levels increased. Both humoral and cellular immune response to MBP were completely suppressed in rats treated with FK506. From these results, it is presumed that immunosuppression of cell-mediated immunity and/or humoral immunity by the treatment of FK506 actually causes the decreased incidence noted in the experiment for the development of EAE.
我们研究了新型免疫抑制剂FK506对大鼠实验性变应性脑脊髓炎（EAE）发病的影响。在完全弗氏佐剂中用髓磷脂碱性蛋白（MBP）免疫的大鼠中，EAE发病率为100%。从免疫当天（第0 - 4天和第7 - 11天）开始，每周5天肌肉注射，持续2周，剂量为1.0毫克/千克/天或更高的FK506可预防EAE的临床症状至少50天，当该化合物给药5天（第0 - 4天）时也得到了类似结果。然而，从免疫后7天开始使用FK506时，其有效性显著但较弱。在EAE出现之前就产生了对MBP的迟发型超敏反应（DTH），并且抗MBP抗体水平升高。用FK506治疗的大鼠对MBP的体液免疫和细胞免疫反应均被完全抑制。从这些结果推测，FK506治疗对细胞介导免疫和/或体液免疫的免疫抑制实际上导致了EAE发病实验中观察到的发病率降低。
