Telbivudine preserves T-helper 1 cytokine production and downregulates programmed death ligand 1 in a mouse model of viral hepatitis.
Telbivudine is an orally bioavailable L-nucleoside with potent and specific anti-hepatitis B virus activity. The higher rate of hepatitis B e antigen (HBeAg) seroconversion during telbivudine treatment than other potent anti-HBV agents suggests a potential immunomodulatory effect. We sought to determine the effects of telbivudine on the immune system, particularly on cytokine production and T-cell response, using an animal model with mouse hepatitis virus strain 3 (MHV-3)-induced hepatitis. The effects of telbivudine on virus replication and cytokine production were investigated in vitro using MHV-3-infected macrophages, and the effects on T-cell response were investigated in vivo in an MHV-3-induced viral hepatitis model. Telbivudine had no effect on MHV-3 replication in macrophages. However, the production of tumour necrosis factor-alpha and interleukin-12 was increased significantly in MHV-3-induced macrophages treated with telbivudine. In vivo survival was enhanced in telbivudine-treated mice, with marked normalization in clinical conditions and histological lesions. Serum levels of interferon-gamma were elevated significantly after telbivudine treatment in MHV-3-infected C3H mice. In contrast, serum interleukin-4 levels were decreased significantly. Furthermore, telbivudine treatment enhanced the ability of T cells to undergo proliferation and secrete cytokines but did not affect cytotoxicity of infected hepatocytes. Of note, we found that telbivudine treatment suppressed programmed death ligand 1 expression on T cells. The results demonstrate the immunomodulatory properties of telbivudine, independent of its antiviral activity, in a mouse model of MHV-3-induced hepatitis.
Wu
Z G
ZG
Department of Infectious Disease, Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yan
W M
WM
Guo
W
W
Chen
T
T
Zou
Y
Y
Wang
H W
HW
Wang
X J
XJ
Yang
X J
XJ
Lu
Y L
YL
Luo
X P
XP
Ning
Q
Q
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage; D060890:B7-H1 Antigen / Q000032:analysis*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy* / Q000276:immunology*; D007155:Immunologic Factors / Q000008:administration & dosage*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D006517:Murine hepatitis virus / Q000187:drug effects; D009705:Nucleosides / Q000008:administration & dosage*; D011744:Pyrimidinones / Q000008:administration & dosage*; D016019:Survival Analysis; D000077712:Telbivudine; D018417:Th1 Cells / Q000737:chemistry / Q000276:immunology*; D013936:Thymidine / Q000031:analogs & derivatives
D000998:Antiviral Agents; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D016207:Cytokines; D007155:Immunologic Factors; D009705:Nucleosides; D011744:Pyrimidinones; D000077712:Telbivudine; D013936:Thymidine