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体外促炎细胞因子释放减少和血浆白细胞介素-6 升高是卒中后谵妄的炎症特征。

Reduced ex vivo release of pro-inflammatory cytokines and elevated plasma interleukin-6 are inflammatory signatures of post-stroke delirium.

机构信息

Department of Neurology, Jagiellonian University Medical College, ul. Botaniczna 3, 31-503, Krakow, Poland.

Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University Medical College, Krakow, Poland.

出版信息

J Neuroinflammation. 2018 Apr 18;15(1):111. doi: 10.1186/s12974-018-1156-y.

DOI:10.1186/s12974-018-1156-y
PMID:29669581
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5907192/
Abstract

BACKGROUND

Experimental studies suggest that systemic inflammation contributes to the pathophysiology of delirium. The aim of our study was to determine blood-derived inflammatory signatures of post-stroke delirium.

METHODS

We included 144 ischemic stroke patients. We assessed delirium on a daily basis during the first 7 days of hospitalization. Venous blood was collected at day 3 after the onset of stroke and stimulated ex vivo with lipopolysaccharide (LPS). We measured LPS-induced cytokine concentration (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12p70) as well as plasma levels of IL-6 and TNFα.

RESULTS

Delirium was diagnosed in 21.5% of patients. After correction for monocyte count, patients with delirium had reduced LPS-induced TNFα, IP-10, IL-1β, IL-6, and IL-12 release. The plasma IL-6 level was higher in delirious patients compared to patients without delirium. After adjusting for stroke severity and infections, higher ex vivo TNFα (OR 0.29, 95%CI 0.11-0.72, P = 0.01), IP-10 (OR 0.25, 95%CI 0.08-0.73, P = 0.01), IL-1β (OR 0.42, 95%CI 0.20-0.89, P = 0.02), and IL-12 (OR 0.07, 95%CI 0.01-0.70, P = 0.02) release was associated with the reduced risk of delirium. In multivariate analysis, the higher plasma IL-6 was associated with the increased risk of delirium (OR 1.61, 95%CI 1.00-2.58, P = 0.04).

CONCLUSIONS

Reduced ex vivo release of pro-inflammatory cytokines after LPS stimulation and the elevated plasma IL-6 are signatures of post-stroke delirium.

摘要

背景

实验研究表明,全身炎症反应与谵妄的病理生理学有关。我们的研究目的是确定中风后谵妄的血液炎症特征。

方法

我们纳入了 144 名缺血性脑卒中患者。在住院的头 7 天内,我们每天对谵妄进行评估。在中风发病后第 3 天采集静脉血,体外用脂多糖(LPS)刺激。我们测量了 LPS 诱导的细胞因子浓度(TNFα、IP-10、IL-1β、IL-6、IL-8、IL-10 和 IL-12p70)以及血浆中 IL-6 和 TNFα 的水平。

结果

21.5%的患者被诊断为谵妄。校正单核细胞计数后,谵妄患者 LPS 诱导的 TNFα、IP-10、IL-1β、IL-6 和 IL-12 释放减少。与无谵妄的患者相比,谵妄患者的血浆 IL-6 水平更高。在调整了中风严重程度和感染后,更高的体外 TNFα(OR 0.29,95%CI 0.11-0.72,P=0.01)、IP-10(OR 0.25,95%CI 0.08-0.73,P=0.01)、IL-1β(OR 0.42,95%CI 0.20-0.89,P=0.02)和 IL-12(OR 0.07,95%CI 0.01-0.70,P=0.02)释放与谵妄风险降低相关。多变量分析显示,血浆中较高的 IL-6 与谵妄的风险增加有关(OR 1.61,95%CI 1.00-2.58,P=0.04)。

结论

LPS 刺激后促炎细胞因子的体外释放减少和血浆中 IL-6 的升高是中风后谵妄的特征。

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