Table 3.

Representative studies demonstrating tissue protective effects of CO in pre-clinical models of inflammatory disease

Model	Target Organ	Species	Phenotype	Ref
Endotoxemia	Systemic	Mice	Increased survival, Reduced pro-inflammatory cytokine production, increased IL-10	45
		Pigs	Reduced coagulation. Reduced pro-inflammatory cytokine production, increased IL-10	46
		Monkeys (Macaques)	Reduced TNF, Reduced Neutropenia	47
Hyperoxic Injury	Lung	Mice	Increased survival, Reduced pro-inflammatory cytokine production	48–49
Mechanical Ventilation	Lung	Rats, Mice	Reduction of BAL protein and cell count, lung neutrophil recruitment, and edema	50–52
Sepsis	Lung, Liver	Mice	Increased survival, increased bacterial clearance from organs and blood, induction of autophagy	53–54
		Baboons	Normalization of pro-resolving mediator profiles	55
Ischemia/Reperfusion	Lung Liver	Mice	Inhibition of apoptosis Reduced inflammation	56–57
Vascular Injury	Vascular Tissue	Mice, Rats	Reduced intimal hyperplasia Reduced inflammation	58
Sickle Cell Disease	Vascular Tissue	Mice	Reduced vascular stasis Reduced lung NF-κB activation	59–60
Organ Transplantation	Lung	Rat	Inhibition of apoptosis and inflammation, reduced macrophage infiltration	61–63
		Swine	Graft tolerance, Inhibition of inflammation	64
	Vascular	Rat	Reduced intimal hyperplasia Reduced inflammation	58, 65
	Heart	Mouse-to-Rat, Rat	Inhibition of platelet aggregation, thrombosis, apoptosis, infarction	66–70
	Kidney	Rat	Improved renal function, survival	67; 71–74
		Swine	Improved graft function, reduced I/R injury	75–76
	Liver	Rat	Reduced I/R injury	77–78
	Intestine	Rat	Reduced I/R injury	79–80
	Pancreas	Rats, Mice	Improved graft survival, Islet function	81–83