These results suggest that SIRT1-mediated hypo-acetylation of HMGB1 attenuates the secretion of proinflammatory cytokines such as TNF-α and IL-6 in endotoxemia, thereby protecting against the LPS-induced clinical manifestations of endotoxemia such as lethargy, diarrhea, and piloerection. This evidence concerns the gene SIRT1 and serum lipopolysaccharide activity.