High-tidal-volume mechanical ventilation can also lead to increase of HMGB1 production, recruitment of neutrophils, and the development of acute lung injury involving activation of phosphoinositide 3-OH kinase (PI 3-K) and serine/threonine kinase/protein kinase B (Akt) in an isolated mouse model of endotoxemia [14]. Here, HMGB1 is linked to serum lipopolysaccharide activity.