Table 3.

Manipulation of DAMP function ameliorates experimental disease. Therapeutic blockade of DAMP function, for example, using monoclonal or polyclonal antibodies (mAb, pAb) or specific inhibitors or silencing DAMP expression by siRNA can reduce disease progression in vivo.

DAMP	Disease Model	Mechanism of blockade	Refs
HA	Lung inflammation (bleomycin)	Over expression of HA synthase improved survival and decreased apoptosis	[145]
	Sepsis (LPS)	High MW HA reduced lung neutrophil infiltration and cytokine synthesis	[146]
HMGB1	Brain injury (transient ischemia)	mAb reduced infarct size and severity, locomotor function, cytokine synthesis	[130]
	Colitis (DSS, TNBS)	pAb, ethyl pyruvate ameliorated disease, reduced cytokine synthesis, associated tumors	[147, 148]
	Lung inflammation (LPS)	pAb decreased neutrophils, lung edema	[136, 138]
	Lung injury (ventilator)	Ab improved oxygenation, neutrophil influx, cytokine synthesis	[149]
	Hepatic ischemia reperfusion injury	pAb decreased liver damage	[135]
	Acute pancreatitis (duodenal loop closure)	pAb improved pancreas and lung damage, aggravated bacterial translocation to pancreas	[150]
	Hemorrhagic shock (blood withdrawal)	pAb improved survival, ameliorated ileal permeability, decreased serum cytokines	[151]
	Hemorrhagic lung injury (cyclo-phosphamide)	pAb reduced pulmonary edema, neutrophil accumulation, lung permeability	[152]
	Sepsis (LPS, E. Coli, cecal ligation and puncture)	pAb, mAb, DNA binding box A protected from/reversed lethality, rescues taste aversion	[114, 129, 153–155]
		Ethyl pyruvate, stearoyl lysophosphatidylcholine, nicotine (inhibit secretion) protected from lethality	[156–158]
		Neural ant-inflammatory peptides vasoactive intestinal peptide and urocortin rescue lethality	[159]
		Cisplatin (nuclear sequestration of HMGB1) protected from lethality	[160]
	Rheumatoid arthritis (Collagen)	pAb, DNA binding box A reduced severity of established joint disease	[161]
HSP90	Rheumatoid arthritis (Collagen, adjuvant)	SNX-7081 (inhibitor) ameliorated disease, joints returned to normal	[162]
	Tumorigenesis (nude mice)	BX-2819 (inhibitor) inhibited tumor growth	[163]
Neutrophil elastase	Acute lung injury (LPS induced)	Sivelestat or L-658,758 (inhibitors) reduced HMGB levels and lung damage	[164, 165]
	Colitis (dextran)	ONO-5046 (inhibitor) reduced disease severity	[166]
	Rheumatoid arthritis (Collagen)	ONO-5046 (inhibitor) reduced incidence and severity of disease, ablated cartilage destruction	[167]
	Hepatic ischemia reperfusion injury	GW311616A (inhibitor) ameliorated liver damage, decreased neutrophil infiltration	[168]
Serum amyloid A	Tumorigenesis (LLC inoculation)	pAb reduced lung metastasis	[169]
Versican	Tumorigenesis (LLC inoculation)	siRNA reduced lung metastasis	[25]