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World J Gastroenterol. Sep 14, 2007; 13(34): 4641-4645
Published online Sep 14, 2007. doi: 10.3748/wjg.v13.i34.4641
Effects of lamivudine on the function of dendritic cells derived from patients with chronic hepatitis B virus infection
Peng-Yuan Zheng, Dong-Yun Zhang, Gao-Feng Lu, Ping-Chang Yang, Yuan-Ming Qi, Bai-Sheng Wang
Peng-Yuan Zheng, Gao-Feng Lu, Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, Henan Province, China
Dong-Yun Zhang, Department of Physiopathology, Luohe Medical College, Luohe 462002, Henan Province, China
Ping-Chang Yang, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
Yuan-Ming Qi, Bai-Sheng Wang, Department of Biological Engineering, Zhengzhou University, Zhengzhou 450052, Henan Province, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Peng-Yuan Zheng, MD, PhD, Professor of Medicine, Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, 2 Jingba Road, Zhengzhou 450014, Henan Province, China. medp7123@yahoo.com
Telephone: +86-371-65261035 Fax: +86-371-63934118
Received: May 16, 2007
Revised: June 2, 2007
Accepted: June 9, 2007
Published online: September 14, 2007
Abstract

AIM: 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 CD1α, 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 CD1α 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).

CONCLUSION: 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.

Keywords: Dendritic cell; Lamivudine; Chronic hepatitis B; Immune