Roberge F G, Xu D, Chan C C, de Smet M D, Nussenblatt R B, Chen H
Laboratory of Immunology, National Eye Institute, Bethesda, MD.
Curr Eye Res. 1993 Feb;12(2):197-203. doi: 10.3109/02713689308999487.
Rapamycin (RAPA) is a macrolide antibiotic with unique immunosuppressive properties. RAPA inhibits T-cell function by interfering with IL-2 and IL-4 signal transduction. It does not prevent IL-2 production or IL-2R expression. The efficacy of RAPA in the treatment of autoimmune diseases was evaluated using the experimental autoimmune uveoretinitis (EAU) model. EAU was actively induced in Lewis rats by immunization with S-antigen in Hunter's adjuvant. RAPA and control vehicle were administered by continuous intravenous infusion over a 14 day period by miniosmotic pump. RAPA treatment initiated on the day of immunization or 7 days later was found to efficiently inhibit EAU induction. The minimal effective dose was 0.1 mg/kg/d. EAU inhibition was correlated with reduced number of cells in the immunization site draining lymph nodes, as well as with a shift and lowering of the peak of the lymphocyte proliferative response curve. The anti-S-antigen antibody response was delayed by 3 days under RAPA treatment and the serum levels lowered in a dose dependent manner. An initial body weight loss was observed during the first week of drug administration, but there was a normal weight gain afterward.
雷帕霉素（RAPA）是一种具有独特免疫抑制特性的大环内酯类抗生素。RAPA通过干扰白细胞介素-2（IL-2）和白细胞介素-4（IL-4）信号转导来抑制T细胞功能。它并不阻止IL-2的产生或IL-2受体的表达。使用实验性自身免疫性葡萄膜视网膜炎（EAU）模型评估了RAPA治疗自身免疫性疾病的疗效。通过在Hunter佐剂中用S抗原免疫，在Lewis大鼠中主动诱导EAU。通过微型渗透泵在14天内持续静脉输注给予RAPA和对照载体。发现在免疫当天或7天后开始的RAPA治疗可有效抑制EAU的诱导。最小有效剂量为0.1mg/kg/d。EAU抑制与免疫部位引流淋巴结中的细胞数量减少相关，也与淋巴细胞增殖反应曲线峰值的偏移和降低相关。在RAPA治疗下，抗S抗原抗体反应延迟3天，血清水平以剂量依赖性方式降低。在给药的第一周观察到初始体重减轻，但之后体重正常增加。
