Cytokine Expression in Dengue Fever and Dengue Hemorrhagic Fever Patients with Bleeding and Severe Hepatitis
Cytokine Expression in Dengue Fever and Dengue Hemorrhagic Fever Patients with Bleeding and Severe Hepatitis
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DOI：
10.4269/ajtmh.19-0487
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发表时间：
2020-05-01
影响因子：
3.3
通讯作者：
Shioda, Tatsuo
中科院分区：
文献类型：
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作者：
Imad, Hisham Ahmed;Phumratanaprapin, Weerapong;Shioda, Tatsuo
登革热是当今世界上最常见的蚊媒黄病毒感染。几个因素共同作用，导致严重感染。其中之一是在感染期间引起短暂病理生理的宿主免疫介质失调。这些介质作用于内皮细胞，增加血管通透性，导致血浆泄漏，损害血流动力学和凝血功能。我们进行了一项前瞻性研究，通过评估泰国曼谷热带病医院住院的成人急性登革热感染中促炎性和抗炎性细胞因子的表达及其与登革热临床表现的关系。我们在2015年和2016年疫情期间对96名住院成人进行了三个感染阶段的细胞因子分析，并对确诊的登革热感染进行了血清分型。7种细胞因子（白细胞介素[IL]-2、IL-4、IL-6、IL-8、IL-10、肿瘤坏死因子α和干扰素γ）的血清浓度使用商业试剂盒（Bio-Plex人细胞因子测定法）一式重复测定。在这项研究中，细胞因子谱提示t -辅助性2反应。大多数患者继发感染，有血浆漏出的患者病毒血症水平高于无血浆漏出的患者。此外，我们观察到出血和肝炎与感染早期IL-8水平显著升高相关。此外，出血伴漏血浆患者感染早期IL-6水平也升高。这些结果提示IL-6和IL-8可能协同作用导致血浆渗漏患者出血。
Dengue is the most common mosquito-borne flaviviral infection in the world today. Several factors contribute and act synergistically to cause severe infection. One of these is dysregulated host immunological mediators that cause transient pathophysiology during infection. These mediators act on the endothelium to increase vascular permeability, which leads to plasma leakage compromising hennodynannics and coagulopathy. We conducted a prospective study to explore the expression of pro- and anti-inflammatory cytokines and how they relate to clinical dengue manifestations, by assessing their dynamics through acute dengue infection in adults admitted to the Hospital for Tropical Diseases, Bangkok, Thailand. We performed cytokine analysis at three phases of infection for 96 hospitalized adults together with serotyping of confirmed dengue infection during the outbreaks of 2015 and 2016. The serum concentrations of seven cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha, and interferon gamma) were measured in duplicate using a commercial kit (Bio-Plex Human Cytokine Assay). In this study, the cytokine profile was suggestive of a T-helper 2 response. Most patients had secondary infection, and the levels of viremia were higher in patients with plasma leakage than those without plasma leakage. In addition, we observed that bleeding and hepatitis were associated with significantly higher levels of IL-8 during the early phases of infection. Furthermore, IL-6 levels in the early phase of infection were also elevated in bleeding patients with plasma leakage. These results suggest that IL-6 and IL-8 may act in synergy to cause bleeding in patients with plasma leakage.