Table 1.

Therapies targeting HMGB1 in preclinical disease models.

Mode of anti-HMGB1	Disease model, effects, and species	References
Anti-HMGB1 antibodies	Endotoxemia: polyclonal anti-HMGB1 antibodies (pAb) treatment improved survival in mice.	[6,47]
	Sepsis induced by cecal perforation: both pAb and monoclonal antibody (mAb) treatment improved survival in mice.	[17,21,55]
	Gastro-intestinal disorders: pAb reversed LPS-induced gut barrier dysfunction in rats; reduced inflammation in murine colitis.	[69,70]
	Pancreatitis: pAb attenuated inflammation in acute pancreatitis in mice.	[74]
	Respiratory disorders: pAb ameliorated LPS-induced acute lung injury; ventilator-induced lung injury; pulmonary fibrosis in mice.	[79–83]
	Arthritis: pAb treatment attenuated arthritis and inflammation in collagen-induced arthritis in rodents.	[87–88]
	Hemorrhagic shock (HS): pAb improved survival and lung function after HS in mice.	[81,99]
	Stroke: MAb or pAb treatment ameliorated brain infarction in rats.	[110,111]
	Ischemia–reperfusion injury: pAb ameliorated hepatic ischemia–reperfusion injury in mice.	[10]
HMGB1 A box	Endotoxemia and sepsis induced by cecal perforation in mice: A box treatment improved survival in these models.	[21]
	Pancreatitis: A box protected organ damage caused by pancreatitis in mice.	[75]
	Respiratory disorders. A box reduced LPS-induced lung injury in mice.	[84]
	Arthritis. A box attenuated collagen-induced arthritis in rodents.	[87]
	Stroke: A box ameliorated ischemia brain damage.	[111]
	Ischemia–reperfusion injury: A box reduced damage in ischemia–reperfusion injury of heart in mice.	[15]
	Transplantation. A box prolonged cardiac allograft survival in rodents.	[113]
Others: blockade of RAGE–HMGB1 signaling	Sepsis induced by cecal perforation: improved survival in mice.	[26,56]
	Gastro-intestinal disorders: ameliorated intestinal barrier function after hemorrhagic shock and resuscitation in mice.	[71]
	Arthritis: reduced severity of arthritis in rodents.	[93]
Reduce nuclear HMGB1 release	Endotoxemia: improved survival, reduced end organ damage in mice.	[51,52,114,115]
	Sepsis induced by cecal perforation: improved survival in mice.	[51,52,57–63]
	Pancreatitis: attenuated organ damage in rodents.	[76–78]
	Arthritis: attenuated arthritis and inflammation in collagen-induced arthritis in rodents.	[94–96]
Polymyxin B filter	Sepsis: improved outcome in sepsis patients and piglets by removing HMGB1 from circulation.	[65,66]
	Respiratory disorder: reduced inflammation in patients with acute respiratory distress syndrome.	[85]
Thrombomodulin	Endotoxemia: improved survival in rodents.	[47]
	Respiratory disorder: ameliorated injury-induced lung injury in mice.	[53,86]
	Arthritis: protected against arthritis in mice.	[97]