Administration of fetuin-A significantly reduced endotoxemia- or sepsis-induced increase of circulating HMGB1 levels at 52 h post endotoxemia (Fig. 4B, top panel) or sepsis (Fig. 4B, bottom panel), suggesting that fetuin-A confers protection by inhibiting systemic accumulation of late proinflammatory mediator of these diseases. The gene discussed is HMGB1; the disease is serum lipopolysaccharide activity.