In an animal model of CLP-induced sepsis, HMGB1-neutralizing monoclonal antibodies (mAbs) [44,168] conferred significant protection even when the first dose was given 24 h after disease onset [23,169,170,171], establishing HMGB1 as a “late” mediator of experimental sepsis with a relatively wider therapeutic window than that offered by early proinflammatory cytokines. This evidence concerns the gene HMGB1 and Sepsis.