Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock
Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock
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DOI：
10.1016/s0140-6736(03)15326-3
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发表时间：
2004-01-17
期刊：
影响因子：
168.9
通讯作者：
Levin, M
中科院分区：
文献类型：
--
作者：
Pathan, N;Hemingway, CA;Levin, M
背景：心肌衰竭在感染性休克复杂的病理生理过程中起着重要作用，并导致器官衰竭和死亡。在脓毒症诱导的炎症过程中，释放抑制心肌收缩功能的特定因子。我们的目的是确定这些介质的心肌抑郁症在脑膜炎球菌感染性shock.Methods我们结合基因表达谱与蛋白质和细胞的方法，以确定血清因子引起的心功能障碍，脑膜炎球菌感染性休克。我们确定了暴露于脑膜炎球菌后血液中显著上调的基因。然后，我们选择了进一步分析这些基因的蛋白质产物具有心肌炎因子的特性，特别是一个12-25 kDa的热稳定蛋白，是释放到血清中发病后不久的脑膜炎球菌infection.Findings我们确定了174个显着上调基因脑膜炎球菌感染的血液：6个编码的蛋白质，是预测的大小和心肌炎因子的特性。其中，白细胞介素6在体外引起显著的心肌抑制。从脑膜炎双球菌血症患者的血清样品和脑膜炎双球菌体外刺激的炎性细胞的上清液中去除白细胞介素6可消除负性肌力活性。此外，血清中的白细胞介素6浓度强烈预测心肌功能障碍的程度和疾病的严重程度在儿童与脑膜炎球菌感染性shock.Interpretation白细胞介素6是一个调解人的心肌抑郁症脑膜炎球菌病。这种细胞因子及其下游介质可能是未来治疗策略的目标。
Background Myocardial failure has a central role in the complex pathophysiology of septic shock and contributes to organ failure and death. During the sepsis-induced inflammatory process, specific factors are released that depress myocardial contractile function. We aimed to identify these mediators of myocardial depression in meningococcal septic shock.Methods We combined gene-expression profiling with protein and cellular methods to identify a serum factor causing cardiac dysfunction in meningococcal septic shock. We identified genes that were significantly upregulated in blood after exposure to meningococci. We then selected for further analysis those genes whose protein products had properties of a myocardial depressant factor-specifically a 12-25 kDa heat-stable protein that is released into serum shortly after onset of meningococcal infection.Findings We identified 174 significantly upregulated genes in meningococcus-infected blood: six encoded proteins that were of the predicted size and had characteristics of a myocardial depressant factor. Of these, interleukin 6 caused significant myocardial depression in vitro. Removal of interleukin 6 from serum samples of patients with meningococcaemia and from supernatants of inflammatory cells stimulated by meningococci in vitro abolished the negative inotropic activity. Furthermore, concentrations in serum of interleukin 6 strongly predicted degree of myocardial dysfunction and severity of disease in children with meningococcal septic shock.Interpretation Interleukin 6 is a mediator of myocardial depression in meningococcal disease. This cytokine and its downstream mediators could be a target for future treatment strategies.