Thijs L G, Hack C E, Strack van Schijndel R J, Nuijens J H, Wolbink G J, Eerenberg-Belmer A J, Van der Vall H, Wagstaff J
Medical Intensive Care Unit, Free University Hospital, Amsterdam, The Netherlands.
J Immunol. 1990 Mar 15;144(6):2419-24.
Therapy with high doses of rIL-2 is complicated by the occurrence of hypotensive reactions and the development of a vascular leakage syndrome (VLS). In four patients, who together received seven cycles of high doses of IL-2 (up to 12 x 10(6) U per m2 per day), and who developed these side effects, we observed an unexpected increase in plasma levels of C3a, indicating activation of the complement system. C3a levels markedly increased during IL-2 therapy from 4 nmol/liter (mean level) before therapy to 23 nmol/liter at the end of the cycle. Activation of C3 occurred via the classical pathway inasmuch as C4a levels also increased during therapy. Mean daily C3a levels correlated with signs of the VLS, such as daily weight gain (p less than 0.001) and albumin levels (inverse correlation, p less than 0.001). In five additional patients, who together received seven cycles of lower doses of IL-2 (2 x 10(6) U per m2 per day) and who did not develop a VLS, only moderate increases in C3a levels (up to 13 nmol/liter) were observed. The highest levels at the first day of the regimen (mean: 7 nmol/liter) occurred 8 h after the IL-2 infusion. Thus, administration of IL-2 induces a dose-dependent activation of the complement system in vivo, which appeared to be related to the development of side effects of this therapy, such as the VLS.
高剂量重组白细胞介素-2（rIL-2）治疗会因低血压反应的发生和血管渗漏综合征（VLS）的发展而变得复杂。在4名共接受7个周期高剂量IL-2（高达每平方米每天12×10⁶单位）治疗且出现这些副作用的患者中，我们观察到血浆C3a水平意外升高，表明补体系统被激活。IL-2治疗期间，C3a水平从治疗前的4纳摩尔/升（平均水平）显著升高至周期结束时的23纳摩尔/升。C3的激活是通过经典途径发生的，因为治疗期间C4a水平也升高。每日平均C3a水平与VLS的体征相关，如每日体重增加（p<0.001）和白蛋白水平（呈负相关，p<0.001）。在另外5名共接受7个周期低剂量IL-2（每平方米每天2×10⁶单位）治疗且未发生VLS的患者中，仅观察到C3a水平适度升高（高达13纳摩尔/升）。治疗方案第一天的最高水平（平均：7纳摩尔/升）在IL-2输注后8小时出现。因此，IL-2的给药在体内诱导了补体系统的剂量依赖性激活，这似乎与该治疗的副作用如VLS的发生有关。
