Table 1.

In vivo evidence for therapeutic targeting of MIF in tissue injury

Tissue	Models	Treatments	Regulated cell types	Cellular source of MIF	Results	References
Kidney	Mice: unilateral ischemia/reperfusion or rhabdomyolysis induced acute kidney injury	MIF knock out	More apoptotic and necroptotic tubular cells, more infiltration of inflammatory cells such as Erhr3 + macrophages, F4/80 + macrophages, dendritic cells, and Ly6G + granulocyte	Unknown	MIF-deficient mice had worse acute tubular injury than wild-type mice	[9, 110]
	Mice: cisplatin or ischemia/reperfusion-induced acute kidney injury	MIF knock out, ribosomal protein S19	Less tubular necrosis, less infiltration of F4/80 + macrophages, CD3 + T cells, and neutrophils	Tubular epithelial cells	MIF-deficient mice had less kidney injury; inhibiting MIF with ribosomal protein S19 could reduce kidney injury	[8, 19]
Liver	Mice: chronical ethanol-induced liver injury	MIF knock out and a MIF inhibitor	More apoptosis of hepatic macrophages	Hepatocytes	MIF-deficient mice had less liver injury compared to wild-type mice	[112, 114]
	Mice: acute ethanol-induced liver injury	MIF knock out and a MIF inhibitor	Do not affect activation of neutrophils and macrophages	Hepatocytes	MIF deletion and MIF inhibition prevented mice from injury	[116]
	Mice concanavalin A-induced liver injury	MIF knock out	Less hepatocyte necrosis and recruitment of activated T cells	Unknown	Deletion of MIF protected mice from liver injury compared to wild-type mice	[115]
	Mice: CCl4 and thioacetamide-induced liver fibrosis	MIF knock out and rmMIF treatment	Suppressed activation of hepatic stellate cells	Unknown	MIF-deficient mice had more fibrosis than wild-type mice	[118]
Brain	Mice: Middle cerebral artery ligation	MIF knock out and rmMIF treatment	More apoptotic neurons	Unknown	MIF-knockout mice had greater infarct size than wild type mice. rmMIF treatment rescued neurons from oxidative stress	[124]
	Mice: Transient middle cerebral artery occlusion	MIF knock out or MIF inhibitor ISO-1	Less neuronal death and more microglia	Cortical parvalbumin-positive interneurons	MIF deficiency or administration of MIF antagonist ISO-1 resulted in a smaller infarct size	[17, 125, 126]
Lung	Mice: cigarette smoke-induced COPD	MIF knock out	More pulmonary apoptosis of endothelial and alveolar epithelial cells	Unknown	MIF-deficient develop aged-related emphysema, exposure to cigarette smoke aggravated this emphysema	[11, 20]
	Mice: ozone-induced COPD	MIF inhibitor ISO-1	Fewer macrophages	Unknown	MIF inhibitor ISO-1 improved lung function in mice exposed to ozone	[128]
	Rats: lipopolysaccharide-induced acute lung injury	MIF antibody	Less LPS-induced neutrophil accumulation in the lungs	Alveolar macrophages and bronchial epithelial cells	MIF antibody protects against lipopolysaccharide-induced acute lung injury	[131]