预防急性同种异体移植物排斥反应的非人类的灵长类动物的肺移植受者:诱导嵌合anti-interleukin-2受体单克隆抗体提高耐受性解决方案使用低剂量的免疫抑制活性的微乳液环孢霉素和40 o - (2-hydroxyethyl)雷帕霉素。

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大白鲟B, Gummert J,贝瑞GJ,基督徒U, Serkova N, Ikonen T,钩L, Legay F,舒勒W, Schreier MH,莫里斯再保险

移植。2000年2月27日,69 (4):488 - 96。

PubMed ID

10708100 (在PubMed

]

文摘

背景:以往的研究猕猴猴肺移植受者,我们表现出显著的免疫抑制效果但减少耐受性与高剂量的联合治疗后微乳液环孢霉素(CsA)和SDZ RAD (40 o - (2-hydroxyethyl)雷帕霉素)。目前的研究旨在比较疗效和耐受性低剂量CsA和高剂量SDZ RAD (CTL组)使用嵌合anti-interleukin-2三联疗法(2)受体(CD25)单克隆抗体(mAb) basiliximab (anti-IL-2受体mAb)诱导疗法(basiliximab:静脉注射5毫克天0和4)+低剂量CsA和低剂量SDZ RAD维护免疫抑制(CD25组)。CsA和anti-IL-2受体马伯药物,减少细胞因子的合成和块IL-2-mediated淋巴细胞刺激,分别。SDZ RAD块淋巴细胞刺激其他细胞因子(例如,IL-15)不被马伯anti-IL-2受体。方法:12单方面进行肺移植。接受者被每日体重评估观察了49天,血像、血液化学,射线照片,肺活检。猴子是安乐死在49天前过度减肥的事件(> 25%)或器官衰竭。目标CsA槽水平100 - 200 ng / ml。目标SDZ CTL的RAD槽水平组(mAb) 20 - 40 ng / ml, CD25组和10 - ng / ml。结果:所有的猴子CD25组需要安乐死早期由于药物中毒的迹象。 In contrast, four monkeys in the CTL group were sacrificed on days 28-35 as a result of excessive weight loss (n=3) and renal functional impairment (n=1). Three recipients in the CD25 group were euthanized on days 36, 38, and 46 as a result of persistent high fever associated with severe rejection. The median animal survival in the CTL group was 32 vs. 46 days in the CD25 group (P<0.04). The only two long-term survivors in the CTL group showed moderate rejection at day 49. The median rejection scores at day 14 (A0) and day 28 (A2) were identical in the two groups, despite the fact that the mean SDZ RAD trough level was significantly lower in the CD25 group (CTL: 38+/-3 ng/ml, CD25: 18+/-2 ng/ml, P<0.0001). After basiliximab levels fell below the minimum therapeutic level (1 mg/ml) on day 28, the median rejection score at day 49 increased to A4 in the CD25 group. CONCLUSION: This is the first study to combine an anti-IL-2 receptor mAb with a drug from the rapamycin class plus CsA. Our study shows that induction therapy with basiliximab enabled SDZ RAD blood levels to be significantly reduced, which led to improved tolerability without the penalty of increased rejection.

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药物靶点

药物	目标	类	生物	药理作用	行动
Basiliximab	白介素2受体β亚基	蛋白质	人类	未知的	抗体	细节