title: Additive inhibition of dendritic cell allostimulatory capacity by alcohol and hepatitis C is not restored by DC maturation and involves abnormal IL-10 and IL-2 induction.
abstract: BACKGROUND
  Excessive alcohol use results in impaired immunity, and it is associated with increased incidence and progression of chronic hepatitis C virus (HCV) infection. Here we investigated the effects of HCV infection and alcohol on myeloid dendritic cells (DC) that are critical in antiviral immunity.
  
  
  METHODS
  Immature and mature DCs were generated from monocytes of chronic HCV infected patients (HCV-DC) and controls (N-DC) with IL-4 plus granulocyte-macrophage colony stimulating factor (GM-CSF) in the presence or absence of alcohol (25 mM). DC allostimulatory capacity was tested in mixed lymphocyte reaction (MLR) and cytokine production by ELISA.
  
  
  RESULTS
  Allostimulatory capacity of HCV-DCs was reduced compared to N-DCs and it was further inhibited by alcohol treatment (p < 0.01). MLR was also decreased with alcohol-treated N-DCs. DC phenotypic markers and apoptosis were comparable between HCV-DCs and N-DCs irrespective of alcohol treatment. However, HCV-DCs and alcohol-treated N-DCs exhibited elevated IL-10 and reduced IL-12 production. Reduced MLR with HCV-DCs and its further inhibition by alcohol coexisted with decreasing IL-2 levels (p < 0.017). DC maturation partially improved but failed to fully restore the reduced allostimulatory function of either alcohol-treated or alcohol-naïve HCV-DCs (p < 0.018).
  
  
  CONCLUSIONS
  Alcohol and HCV independently and together inhibit DC allostimulatory capacity, increase IL-10, reduce IL-12 and IL-2 production that cannot be normalized by DC maturation. HCV and alcohol interact to modulate innate and adaptive immune responses via dendritic cells.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, 01605-2324, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Dolganiuc
authors.forename: Karen
authors.initials: K
authors.lastname: Kodys
authors.forename: Andrea
authors.initials: A
authors.lastname: Kopasz
authors.forename: Christopher
authors.initials: C
authors.lastname: Marshall
authors.forename: Pranoti
authors.initials: P
authors.lastname: Mandrekar
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Szabo
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000276:immunology; D007519:Isoantigens / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D007519:Isoantigens; D016753:Interleukin-10; D000431:Ethanol