Momonaka Hiroshi, Hasegawa Shunji, Matsushige Takeshi, Inoue Hirofumi, Kajimoto Madoka, Okada Seigo, Nakatsuka Kenji, Morishima Tsuneo, Ichiyama Takashi
Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
Brain Dev. 2014 Jun;36(6):484-8. doi: 10.1016/j.braindev.2013.07.001. Epub 2013 Jul 29.
Patients with 2009 pandemic H1N1 influenza-associated encephalopathy (pIE) have been reported in Japan. The most common clinical symptoms of this condition are seizures and progressive coma with high-grade fever. We previously highlighted the cytokine profile of pIE; our results suggest that proinflammatory cytokines play an important role in the pathogenesis. High mobility group box 1 (HMGB1) protein is a late mediator of inflammation or sepsis. However, there are few reports regarding the serum and cerebrospinal fluid (CSF) levels of HMGB1 in pIE patients.
We measured serum and CSF levels of HMGB1 in the following: pIE patients with poor outcomes, pIE patients without neurological sequelae, influenza patients without pIE, and control subjects.
Serum HMGB1 levels were significantly higher in pIE patients with poor outcomes compared to those without neurological sequelae. In contrast, there was no difference in CSF HMGB1 levels among all groups. Regarding pIE patients, we found a significant positive correlation between HMGB1 levels and IL-6 in the serum but not in the CSF.
Our results suggest that HMGB1 protein may be involved in the pathogenesis of pIE and that a high serum, but not CSF, level of inflammatory cytokines plays an important role in the severity of pIE.
日本已报告了2009年甲型H1N1流感相关脑病（pIE）患者。这种疾病最常见的临床症状是癫痫发作和伴有高热的进行性昏迷。我们之前强调了pIE的细胞因子谱；我们的结果表明促炎细胞因子在发病机制中起重要作用。高迁移率族蛋白B1（HMGB1）是炎症或脓毒症的晚期介质。然而，关于pIE患者血清和脑脊液（CSF）中HMGB1水平的报道很少。
我们测定了以下人群血清和脑脊液中HMGB1的水平：预后不良的pIE患者、无神经后遗症的pIE患者、无pIE的流感患者和对照受试者。
与无神经后遗症的pIE患者相比，预后不良的pIE患者血清HMGB1水平显著更高。相比之下，所有组间脑脊液HMGB1水平无差异。对于pIE患者，我们发现血清中HMGB1水平与IL-6之间存在显著正相关，但脑脊液中无此相关性。
我们的结果表明，HMGB1蛋白可能参与了pIE的发病机制，并且血清而非脑脊液中高水平的炎性细胞因子在pIE的严重程度中起重要作用。
