Chronic alcohol-induced liver disease inhibits dendritic cell function.

摘要

BACKGROUND/AIMS: We have compared dendritic cell (DC) function derived from the alcoholic liver disease (ALD) sensitive Long-Evans (LE) and resistant Fischer rat strains to determine if the influence of ethanol on DCs was dependent on ALD. METHODS: The LE and Fischer rats were fed an ethanol-containing or isocaloric control liquid diet for 8 weeks and comparisons were made to LE rats injected with thioacetamide as a liver disease control. DCs were isolated from the spleen after expansion with human Fms-like tyrosine kinase receptor 3 ligand plasmid. Maturation markers CD86, CD80, CD40 and MHC-II were analysed by flow cytometry with or without lipopolysaccharide and poly I:C stimulation. Production of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-12p40 and IL-10 cytokines and the antigen presentation ability of DCs was determined. RESULTS: Only LE rats developed ALD characterized by liver injury, elevated alanine aminotransferase levels and steatosis; CD86 and CD40 expression was decreased in LE but not Fischer rats. Reduced TNF-alpha, IFN-gamma, IL-12, proinflammatory and enhanced IL-10 cytokine production was found in DCs isolated from ethanol-fed LE but not Fischer rats. Allostimulatory activity was reduced in LE compared with the Fischer strain. In contrast, DCs isolated from thioacetamide-induced liver damage displayed a reduction only in IL-12p40; TNF-alpha, IL-10 and IFN-alpha production as well as antigen presenting ability remained intact compared with controls. CONCLUSIONS: ALD sensitive LE rats exhibited characteristics of a suppressed DC phenotype that was not observed following thioacetamide-induced liver disease, which suggests an important role for ALD in altering the host cellular and humoral immune responses.