title: Chronic alcohol-induced liver disease inhibits dendritic cell function.
abstract: OBJECTIVE
  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.
authors: The Department of Medicine, Liver Research Center, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI 02905, USA.
authors: Dechun
authors: D
authors: Feng
authors: Ahmet
authors: A
authors: Eken
authors: Vivian
authors: V
authors: Ortiz
authors: Jack R
authors: JR
authors: Wands
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008108:Liver Diseases, Alcoholic / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans; D013154:Spleen / Q000166:cytology; D013853:Thioacetamide
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D013853:Thioacetamide; D000410:Alanine Transaminase