Parlevliet K J, Bemelman F J, Yong S L, Hack C E, Surachno J, Wilmink J M, ten Berge I J, Schellekens P T
Department of Internal Medicine, University of Amsterdam, The Netherlands.
Transpl Int. 1995;8(2):141-6. doi: 10.1007/BF00344424.
In the present study we prospectively compared side effects occurring in 12 patients after the first administration of low-dose OKT3 (0.5 mg twice daily) induction therapy with those in 10 patients who were treated with a conventional dose of OKT3 (5 mg daily) for acute rejection. We also investigated cytokine release and activation of complement and neutrophils as all of these are held responsible for OKT3-induced side effects. Low-dose OKT3 resulted in a significantly decreased side effects score compared to that after a conventional dose of OKT3 (1.8 vs 5.1, p = 0.0006). Following the first administration of low-dose OKT3, TNF peak levels were significantly lower than after a conventional dose of OKT3. In contrast to our data on conventional dose OKT3 treatment, the first administration of low-dose OKT3 did not induce complement activation as reflected by C3a and C4b/c levels in plasma. Finally, the increase in neutrophil degranulation products lactoferrin and elastase-varies; is directly proportional to 1-antitrypsin was much less following 0.5 mg OKT3 than following 5 mg. We conclude that OKT3-induced toxicity is dose-dependent and is mediated not only by cytokine release but also by activation of complement and neutrophils.
在本研究中，我们前瞻性地比较了12例首次接受低剂量OKT3（0.5mg，每日两次）诱导治疗的患者与10例接受常规剂量OKT3（5mg，每日一次）治疗急性排斥反应的患者所出现的副作用。我们还研究了细胞因子释放以及补体和中性粒细胞的激活情况，因为所有这些都被认为与OKT3诱导的副作用有关。与常规剂量OKT3治疗后相比，低剂量OKT3导致副作用评分显著降低（1.8对5.1，p = 0.0006）。首次给予低剂量OKT3后，肿瘤坏死因子（TNF）峰值水平显著低于常规剂量OKT3治疗后。与我们关于常规剂量OKT3治疗的数据相反，首次给予低剂量OKT3并未诱导补体激活，这可通过血浆中C3a和C4b/c水平反映出来。最后，0.5mg OKT3治疗后中性粒细胞脱颗粒产物乳铁蛋白和弹性蛋白酶的增加与α1-抗胰蛋白酶直接成比例的程度远低于5mg治疗后。我们得出结论，OKT3诱导的毒性是剂量依赖性的，不仅由细胞因子释放介导，还由补体和中性粒细胞的激活介导。
