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.
journal_name
J Gastroenterol Hepatoljournal_title
Journal of gastroenterology and hepatologyauthors
Shiina M,Kobayashi K,Satoh H,Niitsuma H,Ueno Y,Shimosegawa Tdoi
10.1111/j.1440-1746.2003.03329.xsubject
Has Abstractpub_date
2004-05-01 00:00:00pages
558-64issue
5eissn
0815-9319issn
1440-1746pii
JGH3329journal_volume
19pub_type
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