Effect of interleukin-6 blockade on tissue factor-induced coagulation in human endotoxemia
Effect of interleukin-6 blockade on tissue factor-induced coagulation in human endotoxemia
复制标题
DOI：
10.1097/01.ccm.0000126265.08175.be
复制
发表时间：
2004-05-01
影响因子：
8.8
通讯作者：
Jilma, B
中科院分区：
文献类型：
--
作者：
Derhaschnig, U;Bergmair, D;Jilma, B
Objective.临床试验表明，白细胞介素（IL）-6代表了人类脓毒症的预测标志物。此外，IL-6已被提议作为内毒素（脂多糖）诱导的凝血激活的候选介质：在灵长类动物模型中，α IL-6抗体（α IL-6 Ab）几乎消除了脂多糖诱导的凝血激活。因此，我们希望确定α IL-6 Ab（B-E8）是否也可以减弱人中脂多糖诱导的凝血激活。设计：该研究是随机、双盲、安慰剂对照的平行组试验（每组n = 12）。大学医疗中心病人。健康志愿者。干预。健康志愿者随机接受80毫克的单克隆抗IL-6抗体（B-E8）或安慰剂静脉推注前2 ng/kg lipopolysaccharide.Measurements和主要结果：B-E8有效地降低IL-6的生物活性，通过B 9-生物测定法在体外和C反应蛋白的浓度。然而，B-E8没有降低脂多糖诱导的组织因子信使RNA转录或下游凝血变量（凝血酶原片段1 + 2、凝血酶-抗凝血酶III复合物和D-二聚体浓度）的血浆浓度。同样，肿瘤坏死因子-α的浓度，纤溶活性（纤溶酶-抗纤溶酶复合物），内皮细胞活化（可溶性E-选择素），和IL-10不受影响。结论：IL-6似乎不介导早期阶段的脂多糖诱导的凝血激活在人类。
Objective. Clinical trials show that interleukin (IL)-6 represents a predictive marker in human sepsis. Furthermore, IL-6 has been proposed as a candidate mediator for endotoxin (lipopolysaccharide)-induced coagulation activation: In a primate model, an alphaIL-6 antibody (alphaIL-6 Ab) almost abolished lipopolysaccharide-induced coagulation activation. Therefore, we wished to determine if an alphaIL-6 Ab (B-E8) may also attenuate lipopolysaccharide-induced activation of coagulation in humans.Design: The study was a randomized, double blind, placebo-controlled parallel group trial (n = 12 per group).Setting., University medical center.Patients. Healthy volunteers.Interventions. Healthy volunteers were randomized to receive either 80 mg of a monoclonal anti-IL-6 Ab (B-E8) or placebo intravenously before bolus infusion of 2 ng/kg lipopolysaccharide.Measurements and Main Results: B-E8 effectively decreased IL-6 bioactivity as measured by a B9-bioassay in vitro and concentrations of C reactive protein. However, B-E8 did not decrease lipopolysaccharide-induced tissue factor-messenger RNA transcription or plasma concentrations of downstream coagulation variables (prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, and D-dimer concentrations). Similarly, tumor necrosis factor-alpha concentrations, fibrinolytic activity (plasmin-antiplasmin complexes), endothelial activation (soluble E-selectin), and IL-10 were unaffected.Conclusion: IL-6 does not appear to mediate early-phase lipopolysaccharide-induced coagulation activation in humans.