Sterile inflammation in acute liver injury: myth or mystery?

Abstract

Inflammation during liver injury normally serves as a mechanism for cleaning up debris and as a stimulant for regeneration. However, aberrant levels of inflammation can provoke further liver injury and inhibit regeneration through the release of damaging reactive oxygen species. Considerable effort has gone into understanding the mechanisms that control the switch between healthy and pathological inflammation. The identification of a receptor system that detects damage-associated molecular patterns and stimulates inflammation has led to the idea of sterile inflammation. This article will focus on the role of sterile inflammation during liver injury in three models where sterile inflammation has been presumed to mediate a portion of the injury mechanism and its potential relevance for the human pathophysiology.

Keywords:

• acetaminophen hepatotoxicity
• damage-associated molecular patterns
• ischemia–reperfusion injury
• monocytes
• neutrophils
• obstructive cholestasis

Financial & competing interests disclosure

The authors were supported in part by NIH grants: DK070195, DK102142 and AA12916, UL1TR000001; 8 P20 GM103549-07 and 5P20RR021940-07, and ES007079-26A2. BL Woolbright is supported by a postdoctoral fellowship from the ‘Training Program in Environmental Toxicology’, T32 ES007079-26A2, from the National Institute of Environmental Health Sciences. H Jaeschke is supported by NIH R01 grants DK070195, DK102142 and AA12916; and grants from the National Center for Research Resources (5P20RR021940-07) and the National Institute of General Medical Sciences (8 P20 GM103549-07) of the National Institutes of Health. H Jaeschke has also received a CTSA grant from NCATS awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research, grant number: UL1TR000001 (formerly #UL1RR033179). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.