INTERLEUKIN-2 INDUCES ACTIVATION OF COAGULATION AND FIBRINOLYSIS - RESEMBLANCE TO THE CHANGES SEEN DURING EXPERIMENTAL ENDOTOXEMIA
INTERLEUKIN-2 INDUCES ACTIVATION OF COAGULATION AND FIBRINOLYSIS - RESEMBLANCE TO THE CHANGES SEEN DURING EXPERIMENTAL ENDOTOXEMIA
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DOI：
10.1111/j.1365-2141.1992.tb06421.x
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发表时间：
1992-10-01
影响因子：
6.5
通讯作者：
HACK, CE
中科院分区：
文献类型：
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作者：
BAARS, JW;DEBOER, JP;HACK, CE
白细胞介素-2（IL-2）的施用引起其它细胞因子如肿瘤坏死因子（TNF）的释放或产生，通过干扰内皮的抗凝特性，可能会诱导接受该药物的患者进入促凝血状态。因此，我们在14名接受12或18 x 10（6）IU/m2/d IL-2的患者中评估了IL-2对凝血和纤溶的影响。输注15分钟，持续5天。在第一次IL-2输注后以短间隔抽取血液样品。在第一天，凝血酶-抗凝血酶（达特）复合物在IL-2输注后2小时开始增加，在4小时达到峰值水平（n = 14; 11.2+/-6.4 μ g/l nu 49.8+/-49.2 μ g/l，P < 0.01）。纤溶酶α 2抗纤溶酶（PAP）复合物显示出相似的模式，从平均基线值17.5+/-7.6 nmol/l上升到4小时的66.8+/-47.7 nmol（P < 0.01）。4例PAP峰值早于达特峰值。组织纤溶酶原激活物（tPA）从4.9 ± 3.7 mug/l的平均基线值上升到4小时的26.3 ± 13.5 mug/l（P < 0.01）。纤溶酶原激活物抑制物1（派-1）水平在6 h时从59+/-35 mug/l升高至113+/-39 mug/l（P < 0.01）。tPA PAI-1复合物在6 h时从0.15 ± 0.07增加到0.69 ± 0.21nmol/l（P < 0.01）。这些变化与内毒素/TNF给药后观察到的扰动相似。这些异常可能在IL-2治疗诱导的副作用中起作用。
The administration of Interleukin-2 (IL-2) causes the release or generation of other cytokines such as tumour necrosis factor (TNF) which. by disturbing the anticoagulant properties of the endothelium, may induce a procoagulant state in patients receiving this drug.We therefore evaluated the effects of IL-2 on coagulation and fibrinolysis in 14 patients receiving 12 or 18 x 10(6) IU/m2/d of IL-2 given as a 15 min infusion for 5 d. Blood samples were drawn at short intervals after the first IL-2 infusion. The parameters were analysed by way of analysis for repeated measures (F tests rather than t tests).During the first day, thrombin-antithrombin (TAT) complexes started to increase 2 h after the IL-2 infusion, reaching peak levels at 4 h (n = 14; 11.2+/-6.4 ug/l nu 49.8+/-49.2 mug/l, P < 0.01). Plasmin alpha2 antiplasmin (PAP) complexes showed a similar pattern rising from a mean baseline value of 17.5+/-7.6 nmol/l to 66.8+/-47.7 nmol at 4 h (P < 0.01). In four patients the peak of PAP preceeded that of TAT. Tissue plasminogen activator (tPA) rose from a mean baseline value of 4.9+/-3.7 mug/l to 26.3+/-13.5 mug/l at 4 h (P < 0.01). Plasminogen-activator-inhibitor-1 (PAI-1) levels increased from 59+/-35 mug/l to 113+/-39 mug/l at 6 h (P < 0.01). tPA PAI-l complexes increased from 0.15+/-0.07 to 0.69+/-0.21 nmol/l at 6 h (P < 0.01).Our study indicates that IL-2 activates the coagulation and fibrinolytic systems in vivo. The changes resemble the perturbations observed after endotoxin/TNF administration. These abnormalities may play a role in the side-effects induced by IL-2 therapy.