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From the Departments of Pediatric Neurology (Drs. Aiba, Mochizuki, and Hojo) and Allergy and Clinical Immunology (Dr. Kimura), Shizuoka Children’s Hospital, Shizuoka, Japan.
Address correspondence and reprint requests to Dr. Hideo Aiba, Shizuoka Children’s Hospital, 860 Urushiyama, Shizuoka, Japan 420-8660; e-mail: haiba{at}jun.ncvc.go.jp
OBJECTIVE: 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-
(TNF) 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.
METHODS: TNF, IL-6, soluble tumor necrosis factor receptor 1 (sTNF-R1), interferon-
(IFN), 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.
RESULTS: The increases in the serum TNF, 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.
CONCLUSION: The serum IL-6 level may be the most useful indicator for the diagnosis and the clinical severity of influenza virus–associated encephalopathy.
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