HMGB1 has two LPS-binding domains which bind to polysaccharides or lipid A moieties of LPS, and administration of HMGB1 peptides containing these LPS-binding domains was shown to inhibit LPS-HMGB1 binding, HMGB1-mediated LPS transfer to CD14, and LPS-induced tumor necrosis factor-α (TNF-α) release in human peripheral blood mononuclear cells and in a subclinical endotoxemia mouse model24. This evidence concerns the gene TNF and serum lipopolysaccharide activity.