Aiba H, Mochizuki M, Kimura M, Hojo H
Department of Pediatric Neurology, Shizuoka Children's Hospital, Shizuoka, Japan.
Neurology. 2001 Jul 24;57(2):295-9. doi: 10.1212/wnl.57.2.295.
In Japan, >200 children with influenza virus-associated encephalopathy were reported in 1999 and the mortality rate was high. The levels of tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6) in both CSF and serum were significantly increased in severe cases. The authors found a correlation between elevated serum cytokine levels and mortality and neurologic morbidity.
TNFalpha, IL-6, soluble tumor necrosis factor receptor 1 (sTNF-R1), interferon-gamma (IFNgamma), and IL-2 were measured by the ELISA method in sera from six children with encephalopathy before and during therapy, and in six age-matched controls with influenza type A virus infection.
The increases in the serum TNFalpha, IL-6, and sTNF-R1 levels were statistically significant at the onset of symptoms before therapy, but the IL-6 level was most useful for diagnosis. The serum IL-6 levels were >6,000 pg/mL in children with brain stem dysfunction, about 150 pg/mL in children without brain stem dysfunction, and <80 pg/mL in controls. The time course of the serum IL-6 level also reflected the clinical condition. Once the serum IL-6 level was increased to >15,000 pg/mL, none of the children survived. The lower the maximal serum IL-6 level, the milder the CNS sequelae.
The serum IL-6 level may be the most useful indicator for the diagnosis and the clinical severity of influenza virus-associated encephalopathy.
1999年日本报告了200多名患流感病毒相关脑病的儿童,死亡率很高。重症病例的脑脊液和血清中肿瘤坏死因子-α(TNFα)和白细胞介素-6(IL-6)水平均显著升高。作者发现血清细胞因子水平升高与死亡率及神经疾病发病率之间存在关联。
采用酶联免疫吸附测定法(ELISA)检测6例脑病患儿治疗前及治疗期间血清中的TNFα、IL-6、可溶性肿瘤坏死因子受体1(sTNF-R1)、干扰素-γ(IFNγ)和IL-2,并检测6例年龄匹配的甲型流感病毒感染对照者血清中的上述指标。
治疗前症状出现时,血清TNFα、IL-6和sTNF-R1水平的升高具有统计学意义,但IL-6水平对诊断最有用。脑干功能障碍患儿的血清IL-6水平>6000 pg/mL,无脑干功能障碍患儿约为150 pg/mL,对照者<80 pg/mL。血清IL-6水平的时间进程也反映了临床状况。一旦血清IL-6水平升高至>15000 pg/mL,患儿无一存活。血清IL-6最高水平越低,中枢神经系统后遗症越轻。
血清IL-6水平可能是诊断流感病毒相关脑病及评估其临床严重程度最有用的指标。