Table 2.

Representative studies showing CO-dependent protection in inflammation models.

Injury/Disease Model	Species	Dose	Observation	Ref.
LPS	Mice	250 ppm [100–500 ppm] CO	Anti-inflammatory effect, reduction of pro-inflammatory cytokines (TNFα, IL-6), p38 MAPK, JNK, IL-6 dependent. Upregulation of serum IL-10.	[58,114,115,116]
“	Pig	250 ppm	Reduced disseminated intravascular coagulation; Reduction of pro-inflammatory cytokines (IL-1β) and endothelial ICAM expression. Upregulation of IL-10	[94]
“	Macaque	500 ppm CO	Reduction of pro-inflammatory cytokine (TNFα), >30% CO-Hb	[95]
Pneumonia-ALI	Baboon	100–300 ppm CO	Reduction of lung inflammation, improved histology	[96]
Hyperoxia	Rat	250 ppm CO	Reduction of lung edema, inflammation, fibrin deposition, and apoptosis; improved histology.	[59]
“	Mice	250 ppm CO	Reduction of lung inflammation; p38 MAPK-dependent	[60]
VILI	Rat	250 ppm CO	Reduction of lung inflammation, Reduced neutrophil influx	[103]
“	Mice	250 ppm CO	Reduction of lung inflammation, Improved lung histology	[101,102]
MA-ALI/ECM	Mice	CORM (ALF-492 36.7 mg/kg) 50 ppm CO	Improved lung histology and survival/Protection in CM, reduced neuroinflammation.	[117,118,119,120,121]
Hemorrhagic shock	Mice	250 ppm CO CORM3 (4 mg/kg)	Reduced inflammation, apoptosis. Upregulation of IL-10.	[97,98,99]
Sepsis/CLP	Mice	250 ppm CO	Increased autophagy, improved bacterial clearance	[67,100]
“		CORM2 (30 mg/kg)	Reduced HMGB1 expression, Improved survival in sepsis	[79]
Lung I/R	Mice	250 ppm CO	p38 MAPK-dependent anti-inflammatory effects	[66]
Lung transplant	Rat	250–500 ppm	Improved histology, reduction of IRI and pro-inflammatory cytokines (i.e., IL-6); p38 MAPK dependent	[104,105,106]
Kidney transplant	Rat	20 ppm; 250 ppm CO	Improved graft function, reduction of IRI and pro-inflammatory cytokines, improved blood flow. Reduced chronic allograft nephropathy	[108,109,110]
Acute compartment syndrome	Pig	CORM3	Reduced tissue injury, apoptosis, leukocyte activation.	[122]