The proportion of Th17 cells and IL-17 expression levels in peripheral blood of patients with chronic hepatitis B and their clinical significance

doi:10.3969/j.issn.1673-8640.2014.01.004

Abstract

Abstract:

Objective To analyze T helper 17(Th17) cell proportion and interleukin 17(IL-17) levels in peripheral blood of patients with chronic hepatitis B(CHB) and healthy controls, and to evaluate their correlations with disease severity, serum hepatitis B virus(HBV) DNA load and liver injury markers, in order to investigate Th17 cells′ role in the pathogenesis of CHB. Methods The Th17 cell proportion and IL-17 levels in peripheral blood of 93 CHB patients (the mild, moderate and severe CHB patients had 21, 37 and 35 cases, respectively) and 28 healthy controls were determined by flow cytometry and enzyme-linked immunosorbent assay(ELISA). The mRNA expression levels of IL-17 and RAR-related orphan nuclear receptor C (RORC) of purified CD4⁺ T cells after stimulating with anti-CD3 and anti-CD28 antibodies were analyzed by real-time fluorescence polymerase chain reaction(PCR). The IL-17 levels in the supernatant of purified CD4⁺ T cells after stimulating with anti-CD3 and anti-CD28 antibodies were evaluated by ELISA. The data were analyzed statistically, and their relations with serum HBV DNA load, liver injury markers, and so on were analyzed. Results Compared with those of healthy control group, the proportion of Th17 cells in peripheral blood of CHB group was significantly higher, and increased with disease severity. The Th17 cell proportion, IL-17 levels and RORC mRNA levels in severe CHB group were significantly higher than those in moderate and mild CHB groups and healthy control group (P<0.05). There was no statistical significance in serum IL-17 levels among the groups(P>0.05). The IL-17 levels in the supernatant of purified CD4⁺ T cells after stimulating with anti-CD3 and anti-CD28 antibodies from CHB group were significantly higher than those from healthy control group(P<0.05), and the IL-17 levels in the supernatant from severe CHB group were higher than those from moderate and mild groups(P<0.05). The Th17 cell proportion in peripheral blood of CHB group showed a positive correlation with serum alanine aminotransferase(ALT) level (P<0.01), and showed no correlation with serum HBV DNA load. Results The increased Th17 cell proportion in CHB patients may be the one of the factors for liver inflammatory response and liver injury and cause the progression of CHB.

Key words: T helper 17 cell, Interleukin 17, Liver function, Chronic hepatitis B

CLC Number:

R446.63

DING Qingli, TANG Gusheng, HE Zhengwen, SHEN Qian, QIN Yanghua.. The proportion of Th17 cells and IL-17 expression levels in peripheral blood of patients with chronic hepatitis B and their clinical significance[J]. , 2014, 29(1): 15-20.

References

[1] Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection [J]. Nat Rev Immunol, 2005, 5(3): 215-229.
[2] Wu W, Li J, Chen F, et al. Circulating Th17 cells frequency is associated with the disease progression in HBV infected patients [J]. J Gastroenterol Hepatol, 2010, 25(4): 750-757.
[3] Yang W, Ding X, Deng J, et al. Interferon-gamma negatively regulates Th17-mediated immunopathology during mouse hepatitis virus infection [J]. J Mol Med (Berl), 2011, 89(4): 399-409.
[4] 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2010年版) [J]. 肝脏, 2011, 16(1):2-16.
[5] Bian Z, Guo Y, Ha B, et al. Regulation of the inflammatory response: enhancing neutrophil infiltration under chronic inflammatory conditions [J]. J Immunol, 2012, 188(2): 844-853.
[6] Korn T, Bettelli E, Oukka M, et al. IL-17 and Th17 cells [J]. Annu Rev Immunol, 2009, 27:485-517.
[7] Hou W, Kang HS, Kim BS. Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection [J]. J Exp Med, 2009, 206(2): 313-328.
[8] 杨波, 赵彩彦, 王亚东, 等. Th17细胞在慢性乙型肝炎及其重症化中的变化 [J]. 中华传染病杂志, 2012, 30(8): 472-477.
[9] Qi ZX, Wang LY, Fan YC, et al. Increased peri-pheral ROR α and ROR γ mRNA expression is associated with acute-on-chronic hepatitis B liver failure[J]. J Viral Hepat, 2012, 19(11): 811-822.
[10] Zhang JY, Zhang Z, Lin F, et al. Interleukin-17-producing CD4(+) T cells increase with severity of liver damage in patients with chronic hepatitis B [J]. Hepatology, 2010, 51(1): 81-91.
[11] 林振忠, 余雪平, 苏智军, 等. 慢性乙型肝炎患者外周血Treg/Th17比率的检测及其与肝功能的相关性研究 [J]. 中国免疫学杂志, 2012, 28(11):1036-1040.
[12] Ye Y, Xie X, Yu J, et al. Involvement of Th17 and Th1 effector responses in patients with hepatitis B [J]. J Clin Immunol, 2010, 30(4): 546-555.
[13] 徐维家, 李志, 杨婷婷, 等. 系统性红斑狼疮患者Th17和Th1细胞及其细胞因子水平的变化及临床意义 [J]. 检验医学, 2013, 28(5): 396-399.
[14] Du WJ, Zhen JH, Zeng ZQ, et al. Expression of interleukin-17 associated with disease progression and liver fibrosis with hepatitis B virus infection: IL-17 in HBV infection [J]. Diagn Pathol, 2013, 8: 40.
[15] 陈捷, 王兰兰, 付阳, 等. IL-17、IL-23、TGF-β和IL-10在乙型肝炎病毒感染中的表达分析 [J]. 免疫学杂志, 2012, 28(3): 231-236.
[16] 陈晓黎, 吴玮, 侯青顺, 等. T细胞亚群及IL-17与慢性HBV感染结局的关系 [J]. 中国医疗前沿, 2012, 7(5): 1-2.