Moreover, High-mobility group box 1 (HMGB1), a cytokine mediator of lethal systemic inflammation in sepsis and non-sepsis diseases, has been implicated in heatstroke-induced SIRS and direct inhibition of HMGB1 with its monoclonal antibody can decrease circulating inflammatory cytokines [29]. This evidence concerns the gene HMGB1 and systemic inflammatory response syndrome.