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致死性钩端螺旋体病中白细胞介素-6、白细胞介素-17a 和白细胞介素-22 水平升高。

Raised levels of Il-6, Il-17a, and Il-22 in fatal leptospirosis.

机构信息

Department of Medical Laboratory Technology, Faculty of Health Sciences, Universiti Teknologi MARA Cawangan Selangor, Kampus Puncak Alam, 42300, Bandar Puncak Alam, Selangor, Malaysia.

Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia.

出版信息

Eur J Clin Microbiol Infect Dis. 2019 Dec;38(12):2349-2353. doi: 10.1007/s10096-019-03699-5. Epub 2019 Sep 16.

DOI:10.1007/s10096-019-03699-5
PMID:31529307
Abstract

Clinical manifestations of leptospirosis range from mild, common cold-like illness, to a life-threatening condition. The host immune response has been hypothesized to play a major role in leptospirosis outcome. Increased levels of inflammatory mediators, such as cytokines, may promote tissue damage that lead to increased disease severity. The question is whether cytokines levels may predict the outcome of leptospirosis and guide patient management. This study aimed to assess the association between Th1-, Th2-, and Th17-related cytokines with the clinical outcome of patients with leptospirosis. Different cytokine levels were measured in fifty-two plasma samples of hospitalized patients diagnosed with leptospirosis in Malaysia (January 2016-December 2017). Patients were divided into two separate categories: survived (n = 40) and fatal outcome (n = 12). Nineteen plasma samples from healthy individuals were obtained as controls. Cytokine quantification was performed using Simple Plex™ assays from ProteinSimple (San Jose, CA, USA). Measurements were done in triplicate and statistical analysis was performed using GraphPad software and SPSS v20. IL-6 (p = 0.033), IL-17A (p = 0.022), and IL-22 (p = 0.046) were significantly elevated in fatal cases. IL-17A concentration (OR 1.115; 95% CI 1.010-1.231) appeared to be an independent predictor of fatality of leptospirosis. Significantly higher levels of TNF-α (p ≤ 0.0001), IL-6 (p ≤ 0.0001), IL-10 (p ≤ 0.0001), IL-12 (p ≤ 0.0001), IL17A (p ≤ 0.0001), and IL-18 (p ≤ 0.0001) were observed among leptospirosis patients in comparison with healthy controls. Our study shows that certain cytokine levels may serve as possible prognostic biomarkers in leptospirosis patients.

摘要

钩端螺旋体病的临床表现从轻度、普通感冒样疾病到危及生命的疾病不等。宿主的免疫反应被认为在钩端螺旋体病的结果中起主要作用。炎症介质(如细胞因子)水平的升高可能会促进导致疾病严重程度增加的组织损伤。问题是细胞因子水平是否可以预测钩端螺旋体病的结果并指导患者管理。本研究旨在评估 Th1、Th2 和 Th17 相关细胞因子与钩端螺旋体病患者临床结果之间的关系。在马来西亚(2016 年 1 月至 2017 年 12 月)住院诊断为钩端螺旋体病的 52 例血浆样本中测量了不同的细胞因子水平。患者分为两个单独的类别:存活(n=40)和致命结局(n=12)。从 19 名健康个体获得 19 个血浆样本作为对照。使用来自 ProteinSimple(圣何塞,CA,美国)的 SimplePlex™检测试剂盒进行细胞因子定量。测量一式三份进行,使用 GraphPad 软件和 SPSS v20 进行统计分析。在致命病例中,IL-6(p=0.033)、IL-17A(p=0.022)和 IL-22(p=0.046)显著升高。IL-17A 浓度(OR 1.115;95%CI 1.010-1.231)似乎是钩端螺旋体病死亡的独立预测因子。TNF-α(p≤0.0001)、IL-6(p≤0.0001)、IL-10(p≤0.0001)、IL-12(p≤0.0001)、IL17A(p≤0.0001)和 IL-18(p≤0.0001)水平显著升高与健康对照组相比,钩端螺旋体病患者。我们的研究表明,某些细胞因子水平可能是钩端螺旋体病患者的潜在预后生物标志物。

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本文引用的文献

1
Do the Th17 Cells Play a Role in the Pathogenesis of Leptospirosis?辅助性T细胞17在钩端螺旋体病发病机制中起作用吗?
Can J Infect Dis Med Microbiol. 2018 Jul 10;2018:9704532. doi: 10.1155/2018/9704532. eCollection 2018.
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Leptospirosis Pathophysiology: Into the Storm of Cytokines.钩端螺旋体病发病机制:细胞因子风暴。
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Cytokine profile of patients with leptospirosis in Sabah, Malaysia.马来西亚沙巴州钩端螺旋体病患者的细胞因子谱
Pathog Glob Health. 2020 Mar;114(2):99-103. doi: 10.1080/20477724.2020.1724356. Epub 2020 Feb 5.
Med J Malaysia. 2018 Apr;73(2):106-109.
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Effect of Antimicrobial Agents on Inflammatory Cytokines in Acute Leptospirosis.抗菌药物对急性钩端螺旋体病炎症细胞因子的影响。
Antimicrob Agents Chemother. 2018 Apr 26;62(5). doi: 10.1128/AAC.02312-17. Print 2018 May.
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Cytokine levels as biomarkers for leptospirosis patients.细胞因子水平作为钩端螺旋体病患者的生物标志物
Cytokine. 2016 Sep;85:80-2. doi: 10.1016/j.cyto.2016.06.007. Epub 2016 Jun 10.
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Simple Plex(™) : A Novel Multi-Analyte, Automated Microfluidic Immunoassay Platform for the Detection of Human and Mouse Cytokines and Chemokines.简易微流控免疫分析系统(Simple Plex™):一种用于检测人和小鼠细胞因子及趋化因子的新型多分析物自动化微流控免疫分析平台。
Am J Reprod Immunol. 2016 Jun;75(6):678-93. doi: 10.1111/aji.12512. Epub 2016 May 11.
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Cytokines in human leptospirosis.人类钩端螺旋体病中的细胞因子
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9
Severity markers in severe leptospirosis: a cohort study.重症钩端螺旋体病的严重程度标志物:一项队列研究。
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