In summary, HMGB1 contains domains with lipid A- and polysaccharide-binding motifs that can neutralize LPS-mediated TNF-α release in human PBMCs and in a subclinical endotoxemia mouse model; peptides that cover these binding regions may potentially be used as anti-septic therapeutic agents and contribute the survival rate for pathological condition of LPS-mediated sepsis. This evidence concerns the gene TNF and serum lipopolysaccharide activity.