Role of monocytes and macrophages in experimental and human acute liver failure

Table 1 Literature summary on the effect of hepatic macrophage depletion on the extent of liver injury in experimental models of ALF

Study	Model	Method of macrophage depletion/inhibition	Affect on severity of acute liver injury	Conclusion
Laskin et al[18], 1995	APAP (rat)	Gadolinium chloride/dextran sulphate	Decreased ALT at 24 h in treated groups; Decreased necrosis	Macrophage depletion was protective
Michael et al[19], 1999	APAP (mouse)	Gadolinium chloride/dextran sulphate	Decreased ALT at 8 h in treated groups	Macrophage depletion was protective
Hogaboam et al[12], 2000	APAP (mouse)	CCR2 -/-	ALT at 24 and 48 h, hepatic necrosis and TUNEL staining all increased in KO; Increase in IFN-γ and TNF-α	CCR2 KO - macrophage depletion worsened liver injury
Dambach et al[13], 2002	APAP (mouse)	CCR2 -/-	ALT levels similar in WT and KO mice; Histologically KO mice showed less inflammation at 72 h	CCR2 KO - macrophage depletion, caused less inflammation at 72 h but no overall difference in outcome
Ju et al[20], 2002	APAP (mouse)	Liposome/clodronate	Increased ALT at 8 and 24 h in treated group	Macrophage depletion increased liver damage
Holt et al[6], 2008	APAP (mouse)	CCR2 -/-	ALT same at 10 and 24 h; Comparable histological necrosis at 24 h but delayed recovery at 48 and 72 h in CCR2 -/-	Reduction in infiltrating macrophage population causes delayed recovery
Karlmark et al[5], 2009	CCl4 (mouse)	Liposome/clodronate	Unaltered ALT level at 4 and 24 h post-CCl4	Reduction in infiltrating macrophages had no effect on severity of liver damage

ALF: Acute liver failure; ALT: Alanine transaminase; WT: Wild-type; KO: Knockout; APAP: Acetaminophen induced hepatotoxicity; CCl₄: Carbon tetrachloride; CCR2: Chemokine (C-C motif) receptor 2.