Given that (a) endotoxemia stimulates inflammasomes, (b) GSDMD blockade is protective, and (c) HMGB1 is released during endotoxemia, several groups have drawn the conclusion that HMGB1, therefore, is released in vivo by an inflammasome- and GSDMD-dependent mechanism25. This evidence concerns the gene HMGB1 and serum lipopolysaccharide activity.