These results suggest that IR may be an effective factor in combat against HMGB1-related pathologic conditions such as ischemia/reperfusion injury, arthritis, sepsis, or endotoxemia via regulation of the Nrf2/HO-1/HMGB1 pathway, thus leading to the activation of antioxidant mechanisms while inhibiting the release of proinflammatory HMGB1. Here, NFE2L2 is linked to serum lipopolysaccharide activity.