title: Inflammation in alcoholic liver disease.
abstract: Frank Burr Mallory's landmark observation in 1911 on the histopathology of alcoholic liver disease (ALD) was the first identification of a link between inflammation and ALD. In this review, we summarize recent advances regarding the origins and roles of various inflammatory components in ALD. Metabolism of ethanol generates a number of metabolites, including acetate, reactive oxygen species, acetaldehyde, and epigenetic changes, that can induce inflammatory responses. Alcohol and its metabolites can also initiate and aggravate inflammatory conditions by promoting gut leakiness of microbial products, by sensitizing immune cells to stimulation, and by activating innate immune pathways, such as complement. Chronic alcohol consumption also sensitizes nonimmune cells, e.g., hepatocytes, to inflammatory signals and impairs their ability to respond to protective signals. Based on these advances, a number of inflammatory targets have been identified with potential for therapeutic intervention in ALD, presenting new opportunities and challenges for translational research.
authors.affiliation: Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892, USA. wangh4@mail.nih.gov
authors.forename: H Joe
authors.initials: HJ
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.forename: Samir
authors.initials: S
authors.lastname: Zakhari
authors.forename: Laura E
authors.initials: LE
authors.lastname: Nagy
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007155:Immunologic Factors / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000975:Antioxidants; D007155:Immunologic Factors; D018836:Inflammation Mediators