Effects of lamivudine on the function of dendritic cells derived from patients with chronic hepatitis B virus infection.
OBJECTIVE
To investigate if the nucleoside analogue lamivudine (LAM), a potent inhibitor of HBV replication, could restore the function of dendritic cells derived from patients with chronic hepatitis B (CHB) in an Asian population.


METHODS
Dendritic cells (DCs) derived from mononuclearcytes of patients with chronic HBV infection were cultured in the presence of IL-4, granulocyte-macrophage colony-stimulating factors (GM-CSF) and gradient concentrations of LAM (0-2 mmol/L). Cell morphology was observed under light microscopy. Cell surface molecules, including HLA-DR, CD80, CD83, and CD1alpha, were analyzed with flow cytometry. The concentrations of IL-6 and IL-12 in the supernatant were assayed by ELISA. T cell proliferation was assayed by methyl thiazolyl tetrazolium (MTT).


RESULTS
The expression of CD1alpha on DC treated with 0.5 mmol/L LAM (LAM-DC 0.5 mmol/L) was significantly higher than that of DC untreated with LAM (54.1 +/- 4.21 vs 33.57 +/- 3.14, P < 0.05), and so was the expression of CD83 (20.24 +/- 2.51 vs 12.83 +/- 2.12, P < 0.05) as well as the expression of HLA-DR (74.5 +/- 5.16 vs 52.8 +/- 2.51, P < 0.05). Compared with control group, LAM-DC group (0.5 mmol/L) secreted significantly more IL-12 (910 +/- 91.5 vs 268 +/- 34.3 pg/mL, P < 0.05), had lower levels of IL-6 in the culture supernatant (28 +/- 2.6 vs 55 +/- 7.36 pg/mL, P < 0.05), markedly enhanced the stimulatory capacity in the allogeneic mixed leukocyte reaction (MLR) (1.87 +/- 0.6 vs 1.24 +/- 0.51, P < 0.05).


CONCLUSIONS
The lower expression of phenotypic molecules and impaired allogeneic mixed lymphocyte reaction function of dendritic cells derived from patients with HBV infection could be restored in vitro by incubation with LAM.
Zheng
Peng-Yuan
PY
Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. medp7123@yahoo.com
Zhang
Dong-Yun
DY
Lu
Gao-Feng
GF
Yang
Ping-Chang
PC
Qi
Yuan-Ming
YM
Wang
Bai-Sheng
BS
D015703:Antigens, CD / Q000378:metabolism; D001208:Asia; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000821:virology; D004305:Dose-Response Relationship, Drug; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000254:growth & development; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D015703:Antigens, CD; D006513:Hepatitis B e Antigens; C508600:IL6 protein, human; D015850:Interleukin-6; D018894:Reverse Transcriptase Inhibitors; D018664:Interleukin-12; D019259:Lamivudine