14th ICID - Poster Abstracts - International Society for Infectious ...

When citing these abstracts please use the following reference:
Author(s) of abstract. Title of abstract [abstract]. Int J Infect Dis 2010;14S1: Abstract number.
Please note that the official publication of the International Journal of Infectious Diseases 2010, Volume 14, Supplement 1
is available electronically on http://www.sciencedirect.com
Final Abstract Number: 73.013
Session: Animal Models, Pathogenesis & Host Defenses
Date: Friday, March 12, 2010
Time: 12:30-13:30
Room: Poster & Exhibition Area/Ground Level
Type: Poster Presentation
Telbivudine preserves Th1 cytokine response and down regulates PD-L1 in MHV-3–induced viral
hepatitis model
Z. Wu 1 , W. Yan 1 , W. Guo 1 , Y. Zou 1 , H. Wang 1 , X. Wang 1 , X. Yang 1 , Y. Lu 1 , X. Luo 2 , Q. Ning 1
1 Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan,
Hubei, China, 2 Tonji Hospital, Wuhan, China
Background: Telbivudine is an orally bioavailable L-nucleoside with potent and specific anti–
hepatitis B virus (HBV) activity. Recent studies have suggested a potential immunomodulatory
effect of telbivudine. To address this, we sought to determine the effect of telbivudine on the
immune system, particularly cytokine production and T-cell response, in the mouse hepatitis virus
strain 3 (MHV-3)-induced hepatitis model.
Methods: The effect of telbivudine on virus replication and cytokines production in MHV-3
infected macrophages were investigated. In vivo the T cell response to Telbivudine treatment
were also studied in MHV-3 induced viral hepatitis model.
Results: In vitro there was no significant difference in MHV-3 replication in macrophages with or
without telbivudine treatment. The production of tumor necrosis factor– and interleukin-12 was
increased significantly in MHV-3–induced macrophages with telbivudine treatment. In vivo
survival was enhanced in telbivudine-treated mice with marked normalization in clinical conditions
and histologic lesions. Serum levels of interferon- were elevated significantly after telbivudine
treatment in MHV-3–infected C3H mice. In contrast, serum interleukin-4 levels were decreased
significantly. Furthermore, telbivudine treatment had a beneficial effect on T cells, restoring their
ability to undergo proliferation and secrete cytokines but not to enhance cytotoxicity on infected
hepatocytes. Notably, we found that telbivudine treatment suppressed programmed death ligand
1 expression on T cells.
Conclusion: These data identify an immunomodulatory mechanism of telbivudine treatment in
the MHV-3–induced viral hepatitis model and provide insights into a potential additional mode of
action for the management of viral hepatitis infection.