Ethanol inhibition: the humoral and cellular immune response to hepatitis C virus NS5 protein after genetic immunization

Alcohol Clin Exp Res. 2000 Jul;24(7):1063-9.

Abstract

Background: The combination of chronic hepatitis C virus (HCV) and ethanol may increase viral replication, impair cellular immunity, and result in severe and progressive liver disease. Because HCV nonstructural proteins play a major role in viral elimination, we examined the cellular and humoral immune responses after genetic immunization against NS5 in a chronic ethanol mouse model.

Methods: Mice were fed an ethanol or isocaloric pair-fed control liquid diet and were immunized with HCV NS5-expression plasmid.

Results: The humoral and cellular arms of the immune system were significantly impaired in ethanol-fed mice. Abstinence partially reversed the inhibitory effects on antibody levels and the CD4+ proliferative immune response but did not restore the CD8+ cytotoxic T-cell response to this HCV nonstructural protein. Furthermore, we determined whether murine interleukin-2 coadministration with the NS5 expression plasmid would reverse the inhibitory effects of chronic ethanol consumption; again, partial restoration was observed for B-cell and CD4+ T-cell activity, but not for cytotoxic T cells.

Conclusions: These results suggest that the high rate of chronic HCV infection in alcoholics may be due to ethanol's effects on antiviral immune responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Central Nervous System Depressants / pharmacology*
  • Cytokines / drug effects*
  • Cytokines / metabolism
  • Ethanol / pharmacology*
  • Hepatitis C Antibodies / immunology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Cells, Cultured
  • Vaccines, DNA / genetics
  • Vaccines, DNA / pharmacology
  • Viral Nonstructural Proteins / immunology*
  • Viral Nonstructural Proteins / metabolism

Substances

  • Central Nervous System Depressants
  • Cytokines
  • Hepatitis C Antibodies
  • NS-5 protein, hepatitis C virus
  • Vaccines, DNA
  • Viral Nonstructural Proteins
  • Ethanol