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颅内动脉瘤性蛛网膜下腔出血患者的系统性白细胞介素-6 水平升高是蛛网膜下腔出血后并发症的非特异性标志物。

Elevated Systemic IL-6 Levels in Patients with Aneurysmal Subarachnoid Hemorrhage Is an Unspecific Marker for Post-SAH Complications.

机构信息

Department of Neurosurgery, University Hospital Bonn, D-53127 Bonn, Germany.

Department of Pharmaceutics, University of Bonn, D-53121 Bonn, Germany.

出版信息

Int J Mol Sci. 2017 Dec 1;18(12):2580. doi: 10.3390/ijms18122580.

Abstract

Aneurysmal subarachnoid hemorrhage (aSAH) is still a fatal and morbid disease, although bleeding aneurysms can be secured in almost all cases. Occurrence of post-SAH complications including cerebral vasospasm, delayed cerebral ischemia, hydrocephalus, epilepsy, and infections are the main determinants of clinical outcome. Hence, it is important to search for early predictors for specific post-SAH complications to treat these complications properly. Both cellular and molecular (cytokines) inflammation play a key role after aSAH during the phase of occurrence of post-SAH complications. Interleukin-6 (IL-6) is a well-known cytokine that has been extensively analyzed in cerebrospinal fluid (CSF) of patients after aSAH, but detailed studies exploring the role of systemic IL-6 in aSAH associated complications and its impact on early clinical outcome prediction are lacking. The current study aims to analyze the systemic IL-6 levels over two weeks after bleeding and its role in post-SAH complications. We recruited 80 aSAH patients prospectively who underwent peripheral venous blood withdrawal in serum gel tubes. The blood was centrifuged to harvest the serum, which was immediately frozen at -80 °C until analysis. Serum IL-6 levels were quantified using Immulite immunoassay system. Patient records including age, gender, post-SAH complications, aneurysm treatment, and clinical outcome (modified Rankin scale and Glasgow outcome scale) were retrieved to allow different subgroup analysis. Serum IL-6 levels were significantly raised after aSAH compared to healthy controls over the first two weeks after hemorrhage. Serum IL-6 levels were found to be significantly elevated in aSAH patients presenting with higher Hunt and Hess grades, increasing age, and both intraventricular and intracerebral hemorrhage. Interestingly, serum IL-6 was also significantly raised in aSAH patients who developed seizures, cerebral vasospasm (CVS), and chronic hydrocephalus. IL-6 levels were sensitive to the development of infections and showed an increase in patients who developed pneumoniae. Intriguingly, we found a delayed increase in serum IL-6 in patients developing cerebral infarction. Finally, IL-6 levels were significantly higher in patients presenting with poor clinical outcome in comparison to good clinical outcome at discharge from hospital. Serum IL-6 levels were elevated early after aSAH and remained high over the two weeks after initial bleeding. Serum IL-6 was elevated in different aSAH associated complications, acting as a non-specific marker for post-SAH complications and an important biomarker for clinical outcome at discharge.

摘要

颅内动脉瘤性蛛网膜下腔出血(aSAH)仍然是一种致命和致残的疾病,尽管几乎所有情况下都可以安全处理出血性动脉瘤。蛛网膜下腔出血后并发症的发生,包括脑血管痉挛、迟发性脑缺血、脑积水、癫痫和感染等,是临床结局的主要决定因素。因此,寻找特定蛛网膜下腔出血后并发症的早期预测指标以适当治疗这些并发症非常重要。细胞和分子(细胞因子)炎症在蛛网膜下腔出血后发生蛛网膜下腔出血后并发症的阶段发挥关键作用。白细胞介素-6(IL-6)是一种众所周知的细胞因子,在蛛网膜下腔出血患者的脑脊液(CSF)中已广泛分析,但详细研究探索全身 IL-6 在与蛛网膜下腔出血相关的并发症中的作用及其对早期临床结局预测的影响还很缺乏。本研究旨在分析出血后两周内的全身 IL-6 水平及其在蛛网膜下腔出血后并发症中的作用。我们前瞻性地招募了 80 例蛛网膜下腔出血患者,在血清凝胶管中进行外周静脉血采集。采集的血液离心以收获血清,血清立即在-80°C 冷冻直至分析。使用 Immulite 免疫测定系统定量血清 IL-6 水平。检索患者记录,包括年龄、性别、蛛网膜下腔出血后并发症、动脉瘤治疗和临床结局(改良 Rankin 量表和格拉斯哥结局量表),以允许进行不同的亚组分析。与出血后两周内的健康对照组相比,蛛网膜下腔出血后血清 IL-6 水平显著升高。研究发现,Hunt 和 Hess 分级较高、年龄较大、伴有脑室和脑内出血的蛛网膜下腔出血患者的血清 IL-6 水平显著升高。有趣的是,蛛网膜下腔出血患者发生癫痫发作、脑血管痉挛(CVS)和慢性脑积水时,血清 IL-6 也显著升高。IL-6 水平对感染的发生敏感,并在发生肺炎的患者中升高。有趣的是,我们发现发生脑梗死的患者血清 IL-6 延迟升高。最后,与出院时临床结局良好的患者相比,临床结局较差的患者血清 IL-6 水平显著升高。蛛网膜下腔出血后早期血清 IL-6 水平升高,出血后两周内持续升高。血清 IL-6 在不同的蛛网膜下腔出血相关并发症中升高,是蛛网膜下腔出血后并发症的非特异性标志物,也是出院时临床结局的重要生物标志物。

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