HMGB1 and serum lipopolysaccharide activity: Serum levels of HMGB1 significantly increase 16 to 32 hours following systemic lipopolysaccharide challenge in mice, and a systemic injection of the recombinant HMGB1 in mice is lethal, two findings that provide further support for the pathogenic role of HMGB1 in endotoxemia [4].