Sun Guilian, Ota Chiharu, Kitaoka Setsuko, Chiba Yoko, Takayanagi Masaru, Kitamura Taro, Yamamoto Katsuya, Fujie Hiromi, Mikami Hitoshi, Uematsu Mitsugu, Hino-Fukuyo Naomi, Munakata Mitsutoshi, Kure Shigeo, Haginoya Kazuhiro
Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan; Department of Pediatrics, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan; Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai, Japan.
J Neurol Sci. 2015 Feb 15;349(1-2):190-5. doi: 10.1016/j.jns.2015.01.017. Epub 2015 Jan 21.
We examined serum levels of various cytokines, chemokines, growth factors, and adhesion molecules in patients with uncomplicated influenza (n=20) and influenza virus-associated encephalopathy (IE) (n=18) to understand the underlying mechanism of IE. We found that IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, G-CSF, GM-CSF, TNF-α, TIMP-1, MMP-9, sE-selectin, and neutrophil elastase were elevated significantly in sera from patients with uncomplicated influenza and those with IE, compared with normal controls (n=20). Of note, neutrophil elastase, sE-selectin, IL-8, and IL-13 were elevated significantly in IE as compared with uncomplicated influenza. In the present study, for the first time, we found that serum levels of neutrophil elastase were increased in patients with IE compared with uncomplicated influenza, which suggested that cerebral endothelial damage in the development of IE was mediated by neutrophil elastase. The present study implied that anti-elastase agents are possibly an effective therapeutic protocol for IE, but this needs further elucidation.
我们检测了单纯性流感患者（n = 20）和流感病毒相关脑病（IE）患者（n = 18）血清中各种细胞因子、趋化因子、生长因子和黏附分子的水平，以了解IE的潜在机制。我们发现，与正常对照组（n = 20）相比，单纯性流感患者和IE患者血清中的白细胞介素-1β（IL-1β）、白细胞介素-2（IL-2）、白细胞介素-5（IL-5）、白细胞介素-6（IL-6）、白细胞介素-7（IL-7）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、白细胞介素-13（IL-13）、粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、肿瘤坏死因子-α（TNF-α）、基质金属蛋白酶组织抑制因子-1（TIMP-1）、基质金属蛋白酶-9（MMP-9）、可溶性E选择素（sE-selectin）和中性粒细胞弹性蛋白酶均显著升高。值得注意的是，与单纯性流感相比，IE患者血清中的中性粒细胞弹性蛋白酶、sE-选择素、IL-8和IL-13显著升高。在本研究中，我们首次发现，与单纯性流感患者相比，IE患者血清中的中性粒细胞弹性蛋白酶水平升高，这表明IE发生过程中的脑内皮损伤是由中性粒细胞弹性蛋白酶介导的。本研究表明，抗弹性蛋白酶药物可能是治疗IE的有效方案，但这需要进一步阐明。
