In light ofthe secretion of HMGB-1 into the extracellular milieu at this later time point,it will be worthwhile to determine whether the second inflammatory burst andthe upregulation of costimulatory molecules, such as CD86, CD40, as well asHLA-DR (which peaked at 48 hours) [23], are in direct response to the secretion of HMGB-1 that isconsidered the late mediator of sepsis [24]. The gene discussed is CD40; the disease is Sepsis.