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
Department of Medicine, Rheumatology Division; Department of Medicine, Division of Gastroenterology
Medical Subject Headings
Adult; Alcohol Drinking; Cell Differentiation; Dendritic Cells; Ethanol; Female; Hepatitis C; Humans; Immunosuppression; Interleukin-10; Interleukin-2; Isoantigens; Male; Middle Aged; Myeloid Cells; Statistics, Nonparametric; T-Lymphocytes
Gastroenterology | Hepatology | Rheumatology
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-naive 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.
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Citation: Alcohol Clin Exp Res. 2003 Jun;27(6):1023-31. Link to article on publisher's site