In line with this notion, the deacetylation-mediated interaction of HMGB1 and SIRT1 in mice was sufficiently potent to robustly protect against endotoxemia in response to LPS challenge by inhibiting the secretion of HMGB1 and cytokines such as TNF-α and IL-6. Here, SIRT1 is linked to serum lipopolysaccharide activity.