Related Experiment Video
Updated: Aug 4, 2026
Measuring Influenza Neuraminidase Inhibition Antibody Titers by Enzyme-linked Lectin Assay
Published on: September 6, 2016
Predictive value of serum interleukin-6 level in influenza virus-associated encephalopathy
H Aiba1, M Mochizuki, M Kimura
1Department of Pediatric Neurology, Shizuoka Children's Hospital, Shizuoka, Japan. haiba@jun.ncvc.go.jp
Insights
Elevated serum interleukin-6 (IL-6) levels indicate severe influenza virus-associated encephalopathy in children. Higher IL-6 levels correlate with increased mortality and neurological damage, making IL-6 a key diagnostic marker.
Area of Science:
- Pediatric Neurology
- Infectious Diseases
- Immunology
Background:
- Influenza virus-associated encephalopathy (IAE) poses a significant mortality risk in children.
- Elevated pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6), are observed in severe IAE cases.
Purpose of the Study:
- To investigate the diagnostic and prognostic value of serum cytokine levels in children with IAE.
- To establish correlations between specific cytokine levels and clinical severity, mortality, and neurological outcomes.
Main Methods:
- Serum samples from children with IAE and influenza A controls were analyzed using ELISA.
- Measurements included TNFalpha, IL-6, soluble TNF receptor 1 (sTNF-R1), interferon-gamma (IFNgamma), and IL-2.
- Cytokine levels were assessed before and during therapy, and correlated with clinical presentation.
Main Results:
- Serum levels of TNFalpha, IL-6, and sTNF-R1 were significantly elevated in IAE patients before treatment.
- Serum IL-6 levels demonstrated the strongest correlation with disease severity, distinguishing between children with and without brain stem dysfunction.
- A maximal serum IL-6 level exceeding 15,000 pg/mL was associated with non-survival, while lower levels correlated with milder central nervous system (CNS) sequelae.
Conclusions:
- Serum IL-6 is a highly valuable biomarker for diagnosing and assessing the clinical severity of IAE.
- Monitoring serum IL-6 levels can aid in predicting patient outcomes and guiding therapeutic interventions.
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 (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.
Methods:
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.
Results:
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.
Conclusion:
The serum IL-6 level may be the most useful indicator for the diagnosis and the clinical severity of influenza virus-associated encephalopathy.
