α-干扰素治疗慢性乙型肝炎患者外周血单个核细胞TLR4表达和血清Th1/Th2型细胞因子的变化*

doi:10.3969/j.issn.1672-5069.2012.04.015

实用肝脏病杂志 ›› 2012, Vol. 15 ›› Issue (4): 315-317.doi: 10.3969/j.issn.1672-5069.2012.04.015

α-干扰素治疗慢性乙型肝炎患者外周血单个核细胞TLR4表达和血清Th1/Th2型细胞因子的变化^*

李文莉, 吴茂盛, 黄育波, 刘细玲, 朱计芬, 许瑞荣

510317 广州市广东省第二人民医院感染病科

收稿日期:2012-01-12 出版日期:2012-08-10 发布日期:2017-03-15
作者简介:第一作者：李文莉女,34岁,硕士研究生,主治医师。主要从事慢性乙型肝炎的诊治工作。E-mail：liwenli-1978@163.com
基金资助:
2010年广东省发展领域科技计划项目

The change of toll-like receptor 4 on peripheral blood mononuclear cells and the serum Thl/Th2 cytokine levels in patients with chronic hepatitis B receiving interferon-α therapy

Li Wenli, Wu Maosheng, Huang Yubo, et al.

Department of Infectious Diseases,Second Provincial People’s Hospital,Guangzhou 510317,China

Received:2012-01-12 Online:2012-08-10 Published:2017-03-15

摘要/Abstract

摘要： 目的探讨慢性乙型肝炎患者在α-干扰素治疗前后外周血单个核细胞Toll样受体4（TLR4）的表达及血清Thl/Th2型细胞因子水平的变化及其临床意义。方法50例HBeAg阳性慢性乙型肝炎患者予以普通α-干扰素治疗。在治疗前及治疗后3月和6月,使用流式细胞仪检测外周血单个核细胞表面TLR4表达;采用ELISA法检测血清IFN-γ和IL-4水平,并同时检测ALT、HBV DNA水平。结果在治疗3个月和6个月时,早期应答组和无应答组患者血清IFN-γ水平均升高,IL-4水平均降低;两组TLR4水平较治疗前均下降,但应答组患者TLR4下降更明显,有显著性差异（P<0.05）;IFN-γ和IL-4的变化与TLR4的变化无明显相关（P均>0.05）,TLR4与ALT呈正相关（r=0.78,P<0.01）,TLR4的变化与HBV DNA变化无相关（P>0.05）。结论在干扰素-α治疗后,慢性乙型肝炎患者Thl/Th2型细胞因子的变化可能与TLR4表达的变化无相关,而对干扰素治疗的疗效可能与TLR4表达的变化有关。

关键词: 慢性乙型肝炎, 干扰素-α, Toll样受体-4, Thl/Th2细胞因子

Abstract: Objective To investigate the change of toll-like receptor 4 on peripheral blood mononuclear cells and the serum Thl/Th2 cytokine levels in patients with chronic hepatitis B receiving interferon-α therapy. Methods 50 patients with chronic hepatitis B were treated with interferon α for six months. After 12 weeks,they were devided into response and non-response group. Serum HBV DNA was detected by PCR;The Thl/Th2 cytokines were measured by ELISA;TLR4 was measured by flow cytometry. Results The IL-4 and TLR4 contents in the two groups at 3rd and 6th month were significantly lower than that before interferon-α therapy（P<0.05）,while serum IFN-γ levels were higher than that before interferon therapy（P<0.05）;The levels of IFN-γ,IL-4,TLR4,HBV DNA and ALT at 3rd month were significantly different between the two groups（P<0.05）;The levels of IFN-γ and IL-4 in 50 patients were not correlated with TLR4 level（P<0.05）;The change of TLR4 level in response patients at 3rd month was not correlated with the change of HBV DNA levels（P>0.05）. Conclusions The changes of IFN-γ and IL-4 level in CHB patients received 12 week interferon-α therapy may be not releted to the changes of TLR4 level;the changes of TLR4 level probably is releted to the early response in CHB patients received interferon-α therapy.

Key words: Chronic hepatitis B, Interferon -α, Toll-like receptor 4, Thl/Th2 cytokines

李文莉, 吴茂盛, 黄育波, 刘细玲, 朱计芬, 许瑞荣. α-干扰素治疗慢性乙型肝炎患者外周血单个核细胞TLR4表达和血清Th1/Th2型细胞因子的变化^*[J]. 实用肝脏病杂志, 2012, 15(4): 315-317.

Li Wenli, Wu Maosheng, Huang Yubo, et al.. The change of toll-like receptor 4 on peripheral blood mononuclear cells and the serum Thl/Th2 cytokine levels in patients with chronic hepatitis B receiving interferon-α therapy[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2012, 15(4): 315-317.

参考文献

[1] Akira S,Takeda K,Kaisho T,et a1.Toll-like receptors:critical protein linking innate and acquired immunity. Nat Immunol,2001,2:675-680.
[2] 李红霞,潘晨,陈立,等. Toll样受体与慢性乙型肝炎的研究进展. 国际流行病学传染病学杂志,2010,37（3）：195-198.
[3] Lu YC,Yeh WC,Ohashi PS,et a1. LPS/TLR4 signal transduction pathway. Cytokine,2008,42（2）:145-151.
[4] Lian JQ,Wang XQ,Zhang Y,et a1. Correlation of circulating TLR2/4 expression with CD3 + /4 + /8 + T cells and Treg cells in HBV related liver cirrhosis. Viral Immunol,2009,22（5）:301-308.
[5] Shen H,Zhnag M,Minuk GY,et a1. Different effects of rat interferon alpha,beta and gamma on rat hepatic stellate cell proliferation and activation. BMC Cell Biol,2002,3:9-13.
[6] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南（2010年版）. 实用肝脏病杂志,2011,14（2）：81-89.
[7] Akim S,Hemmi H. Recognition of pathogen associated molecular patterns by TLR family. Immunol Lett,2003,85（2）:85-95.
[8] Medzhitov R,Preston H P,Janeway CA,et a1.A human homologue of the Drosophila Toll protein signaLs activation of adaptive immunity. Nature,1997,388（6640）:394-397.
[9] Xagorari A,Chlichlia K. Toll-like receptors and viruses：induction of innate antiviral immune responses. Open Micmbiol J,2008,2:49-59.
[10] 姚上志,蒲云川,孙形,等. 聚乙二醇干扰素α-2b治疗慢性乙型肝炎的疗效观察. 实用肝脏病杂志,2008,11（6）:404-405.
[11] Machida K,Cheng KT,Sung VM,et a1. Hepatitis C virals induces toll-like receptor 4 expression,leading to enhanced production of beta interferon and interleukin-6.J Virol,2006,80（2）:866-874.
[12] Wu J,Lu M,Meng Z,et a1. Toll-like receptor mediated control of HBV replication by nonparenehymal liver cells in mice.Hepatology,2007,46（6）:1769-1778.
[13] He Q,Graham CS,Durante ME,et a1. Differential expression of toll-like receptor mRNA in treatment non-responders and sustained virologic responders at baseline in patients with chronic hepatitis C. Liver Int,2006,26（9）:1100-1110.
[14] Hammond T,Lee S,Watson MW,et a1. Decreased IFNγ production correlates with diminished production of cytokines by dendritic cells in patients infected with hepatitis C virus and receiving therapy. J Viral Hepat,2011,18（7）:482-492.

[1]	朱凌云, 张茂海, 崔莎莎, 张秋萍. 慢性乙型肝炎患者血清IL-12、IL-18水平和外周血单个核细胞FOXp3基因水平研究^*[J]. 实用肝脏病杂志, 2019, 22(6): 816-819.
[2]	石莹莹, 王元喜. 替比夫定联合阿德福韦酯治疗慢性乙型肝炎患者效果及其对肾功能的影响^*[J]. 实用肝脏病杂志, 2019, 22(6): 820-823.
[3]	闵峰, 黄文琪, 吴卫兵, 张丽, 范荣华. 慢性乙型肝炎患者血清脂肪细胞因子水平变化及其临床意义^*[J]. 实用肝脏病杂志, 2019, 22(6): 824-827.
[4]	张迎明, 申爽, 田飞, 孙园园. IFNL4和IL-28B基因多态性检测评估慢性乙型肝炎患者抗病毒治疗应答价值分析^*[J]. 实用肝脏病杂志, 2019, 22(6): 828-831.
[5]	李传杰, 徐静, 王亮亮, 潘劲劲, 刘波. 恩替卡韦治疗慢性乙型肝炎患者血清HBsAg变化与病毒学应答的相关性研究[J]. 实用肝脏病杂志, 2019, 22(6): 928-929.
[6]	赵协山, 伍春瑢, 王春峰, 余积洁, 何青. 替诺福韦联合安络化纤丸治疗HBeAg阴性慢性乙型肝炎患者疗效及其血清肝纤维化指标的变化研究*[J]. 实用肝脏病杂志, 2019, 22(5): 644-647.
[7]	涂杰霞, 王安娜, 廖若汐. 干扰素α-2b与聚乙二醇干扰素α-2a治疗慢性乙型肝炎患者疗效比较研究*[J]. 实用肝脏病杂志, 2019, 22(5): 648-651.
[8]	高伟, 侯勇. 肝脏硬度值检测诊断慢性乙型肝炎患者肝组织纤维化的效能分析*[J]. 实用肝脏病杂志, 2019, 22(5): 652-655.
[9]	白一春, 邓霁红, 梅小平. 影响聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者疗效的多因素分析^*[J]. 实用肝脏病杂志, 2019, 22(4): 490-493.
[10]	程华, 鞠辉, 宋德顺, 李伟. 慢性乙型肝炎患者血清血管生成素样蛋白2和高尔基体蛋白73水平变化及其诊断显著肝纤维化的效能分析^*[J]. 实用肝脏病杂志, 2019, 22(4): 494-497.
[11]	李高明, 吕必华. 菖郁逍遥散治疗慢性乙型肝炎伴抑郁患者负性情绪和中医证候积分的变化^*[J]. 实用肝脏病杂志, 2019, 22(4): 498-501.
[12]	余英芳, 温生宝. 应用磁共振DWI单指数、双指数和拉伸指数模型参数评估慢性乙型肝炎患者肝纤维化程度效能研究^*[J]. 实用肝脏病杂志, 2019, 22(4): 502-505.
[13]	闫瑞斌, 马淑梅, 卓玛, 乔志忠, 刘潇. 慢性乙型肝炎患者血清MMP-2和TIMP-2水平及超声检查指标评估肝纤维化分期意义探讨^*[J]. 实用肝脏病杂志, 2019, 22(4): 506-509.
[14]	张亚飞, 叶珺, 谢琴秀, 邹桂舟, 李家斌, 李旭, 张振华. 不同医院无创性肝纤维化指标预测慢性乙型肝炎患者肝纤维化效能差异分析^*[J]. 实用肝脏病杂志, 2019, 22(4): 510-513.
[15]	彭思璐, 刘冰, 孙宏, 林剑, 潘志颖, 邓存良. HBV相关慢加急性肝衰竭患者预后及其影响因素分析^*[J]. 实用肝脏病杂志, 2019, 22(4): 545-548.

α-干扰素治疗慢性乙型肝炎患者外周血单个核细胞TLR4表达和血清Th1/Th2型细胞因子的变化^*

The change of toll-like receptor 4 on peripheral blood mononuclear cells and the serum Thl/Th2 cytokine levels in patients with chronic hepatitis B receiving interferon-α therapy

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价