Elevation of HMGB1 was detected considerably later than secretion of acute-phase cytokines (such as TNF and IL-1) and reach a persistent plateau at 16–32 h in LPS-induced endotoxemia models and sepsis patients.165,167 Besides, remarkable elevation of HMGB1 is observed in severe sepsis patients and correlate to disease progression.168,169. Here, HMGB1 is linked to serum lipopolysaccharide activity.