Ribavirin upregulates interleukin-12 receptor and induces T cell differentiation towards type 1 in chronic hepatitis C.

Abstract:

BACKGROUND AND AIM:The mechanisms of ribavirin as an immune modulator have not been fully revealed, contrary to its clinical benefit in chronic hepatitis C. Recently, host immune defense, especially cytotoxic T lymphocytes and T helper cells, have been considered to be closely related to the pathophysiology of chronic viral hepatitis. The aim of the present study was to evaluate the function of ribavirin in cellular immunity. METHODS:Peripheral blood mononuclear cells and total RNA were prepared from chronic hepatitis C patients. To evaluate the polarization of T helper cells, we performed intracellular cytokine assay and quantified the production of key cytokines. mRNA levels of interleukin-12 receptor (IL-12R), interferon (IFN)-gamma and interleukin-4 (IL-4) were measured by real time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:The population of T helper 1 cells increased significantly both in mitogen and hepatitis C virus (HCV) core protein stimulated cells with 0.1 microg/mL of ribavirin. However, the population of T helper 2 cells did not seem to be affected by ribavirin. The level of IL-12R beta2 chain mRNA was also upregulated to 130% after 24 h incubation with 0.1 microg/mL ribavirin (P = 0.037), whereas the beta1 chain did not change significantly under these conditions. In addition, 0.1 microg/mL ribavirin could upregulate the levels of IFN-gamma or IL-4 mRNA in some cases. CONCLUSION:Ribavirin, perhaps by acting directly on CD4+ T cells, induces T cell differentiation towards type 1, depending on the upregulated signal of the IL-12/IL-12R pathway.

authors

Shiina M,Kobayashi K,Satoh H,Niitsuma H,Ueno Y,Shimosegawa T

doi

10.1111/j.1440-1746.2003.03329.x

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

558-64

issue

5

eissn

0815-9319

issn

1440-1746

pii

JGH3329

journal_volume

19

pub_type

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