Ribavirin enhancement of hepatitis C virus core antigen-specific type 1 T helper cell response correlates with the increased IL-12 level.
OBJECTIVE
Combination IFN-a and ribavirin therapy for hepatitis C virus-infected patients has been reported to improve the response rate up to 50%. In this study, we aimed to study further the role of ribavirin in hepatitis C virus-specific immune responses.


METHODS
We immunized mice with hepatitis C virus core protein with or without different concentrations of ribavirin. Forty days after immunization, hepatitis C virus-specific immune responses were followed in these mice.


RESULTS
We found that the mice immunized with core antigen once every 2 weeks and 0.5 mg ribavirin every day showed higher levels of core-specific IgG2 compared with those mice immunized with core antigen only. In addition, core antigen-stimulated spleen cells produced higher levels of T helper type 1 cytokines and the core-specific cytotoxic T cell activity also increased significantly. Furthermore, lipopolysaccharide-stimulated peritoneal cells produced higher levels of IL-12 in ribavirin-treated mice, and peritoneal cells isolated from naive mice also produced significantly higher level of IL-12 when cultured with ribavirin.


CONCLUSIONS
Ribavirin may significantly promote the T helper type 1 immune response in vivo, and, furthermore, the effect of ribavirin on IL-12 level produced by accessory cells may contribute to the T helper type 1 enhancing effect.
Fang
S H
SH
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei.
Hwang
L H
LH
Chen
D S
DS
Chiang
B L
BL
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D005260:Female; D018936:Hepatitis C Antigens / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D012254:Ribavirin / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology*
D000998:Antiviral Agents; D018936:Hepatitis C Antigens; D008070:Lipopolysaccharides; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D018664:Interleukin-12; D012254:Ribavirin; D007371:Interferon-gamma