title: Immune responses against oxidative stress-derived antigens are associated with increased circulating tumor necrosis factor-alpha in heavy drinkers.
abstract: Growing evidence indicates that pro-inflammatory cytokines play a key role in alcoholic liver disease (ALD). This study investigates whether immune response toward oxidative stress-derived antigens could be involved in promoting cytokine production in alcohol abusers. Cytokine profile and circulating IgG against human serum albumin modified by malondialdehyde (MDA-HSA) and against oxidized cardiolipin (Ox-CL) were evaluated in 59 heavy drinkers (HD) with (n=30) or without (n=29) ALD and 34 healthy controls. IgG against MDA-HSA and Ox-CL were significantly higher in HD with ALD than in HD without liver injury or healthy controls. The elevation of these antibodies was associated with higher circulating levels of IL-2 (p=0.005) and TNF-alpha (p=0.001), but not of IL-6 or IL-8. The prevalence of abnormal TNF-alpha was 5-fold higher in HD with oxidative stress-induced IgG than in those without. HD with the combined elevation of both TNF-alpha and oxidative stress-induced IgG had 11-fold (OR 10.7; 95%CI 1.2-97.2; p=0.023) greater risk of advanced ALD than those with high TNF-alpha, but no immune responses. Moreover, the combined elevation of TNF-alpha and lipid peroxidation-derived IgG was an independent predictor of ALD in HD. We propose that immune responses towards oxidative stress-derived antigen promote TNF-alpha production and contribute to liver damage in alcohol abusers.
authors.affiliation: Department of Medical Sciences and Interdepartmental Research Centre for Autoimmune Diseases , University Amedeo Avogadro of East Piedmont, Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Vidali
authors.forename: Johanna
authors.initials: J
authors.lastname: Hietala
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Occhino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ivaldi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sutti
authors.forename: Onni
authors.initials: O
authors.lastname: Niemelä
authors.forename: Emanuele
authors.initials: E
authors.lastname: Albano
mesh_terms: D000428:Alcohol Drinking / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002308:Cardiolipins / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008108:Liver Diseases, Alcoholic / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000276:immunology; D008875:Middle Aged; D018384:Oxidative Stress / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D002308:Cardiolipins; D016207:Cytokines; D007074:Immunoglobulin G; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde