Immune responses against oxidative stress-derived antigens are associated with increased circulating tumor necrosis...

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.