Chronic alcohol-induced liver disease inhibits dendritic cell function

Liver Int. 2011 Aug;31(7):950-63. doi: 10.1111/j.1478-3231.2011.02514.x. Epub 2011 Mar 21.

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.

Publication types

  • Comparative Study

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / metabolism
  • CD40 Antigens / metabolism
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Flow Cytometry
  • Immunohistochemistry
  • Liver Diseases, Alcoholic / immunology*
  • Rats
  • Rats, Inbred F344
  • Rats, Long-Evans
  • Spleen / cytology
  • Thioacetamide

Substances

  • B7-1 Antigen
  • B7-2 Antigen
  • CD40 Antigens
  • Cytokines
  • Thioacetamide
  • Alanine Transaminase