Predictive value of serum interleukin-6 level in influenza virus-associated encephalopathy

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-alpha (TNF alpha) 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 alpha, IL-6, soluble tumor necrosis factor receptor 1 (sTNF-R1), interferon-gamma (IFN gamma), 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 alpha, 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.