Serum Inflammatory Cytokine Levels Correlate with Hand-Foot-Mouth Disease Severity: A Nested Serial Case-Control Study

Background: Hand-food-mouth disease (HFMD) cases can be fatal. These cases develop rapidly, and it is important to predict the severity of HFMD from mild to fatal and to identify risk factors for mild HFMD. The objective of this study was to correlate the levels of serum inflammatory cytokines with HFMD severity. Methods: This study was designed as a nested serial case-control study. The data collected included general information, clinical symptoms and signs, laboratory findings and serum cytokine levels. Results: The levels of IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma in patients with severe HFMD were significantly higher than in mild patients during the 2nd to 5th day after disease onset. The levels of IL-4, IL-6, IL-10 and IFN-gamma increased from the 2nd day to the 4th day and later decreased. The levels of TNF-alpha were high on the first two days and subsequently decreased. The changes of IL-10, TNF-alpha and IFN-gamma in the controls were similar for all cases. The levels of IL-4, IL-6 and IL-17 in the controls were not significantly different with the progression of HFMD. Conclusions: Our findings indicate that the IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma levels correlate with HFMD severity.