This finding is consistent with the results of Wang et al that HMGB1 release occurs 16 to 32 hours after TNF-α, and IL-1 release during endotoxemia.[14] On the contrary, this elevated HMGB1 level may provide a valuable indicator clinically to signal the severity of EV71-induced HFMD. This evidence concerns the gene TNF and serum lipopolysaccharide activity.