Chronic alcohol-induced liver disease inhibits dendritic cell function

Authors

  • Dechun Feng,

    1. The Department of Medicine, Liver Research Center, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA
    Search for more papers by this author
  • Ahmet Eken,

    1. The Department of Medicine, Liver Research Center, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA
    Search for more papers by this author
  • Vivian Ortiz,

    1. The Department of Medicine, Liver Research Center, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA
    Search for more papers by this author
  • Jack R. Wands

    1. The Department of Medicine, Liver Research Center, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA
    Search for more papers by this author

Correspondence
Jack R. Wands, The Department of Medicine, The Liver Research Center, Rhode Island Hospital and Warren Alpert Medical School of Brown University, 55 Claverick St., Fourth Floor, Providence, RI 02905.
Tel: +1 401 444 7441
Fax: +1 401 444 2939
e-mail: jack_wands_md@brown.edu

Abstract

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-α (TNF-α), interferon-γ (IFN-γ), 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-α, IFN-γ, 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-α, IL-10 and IFN-α 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.

Ancillary