Yang Kai, Guan Shi-He, Zhang Hao, Pan Ying, Wu Yuan-Yuan, Wang Ai-Hua, Sun Bei-Bei
Department of Laboratory Medicine, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
Int J Mol Sci. 2014 Nov 17;15(11):21286-98. doi: 10.3390/ijms151121286.
The objective of this study was to analyze the expression levels of IL-8 in serum and liver tissues from patients with chronic hepatitis B (CHB) infection and to investigate whether IL-8 may antagonize interferon-alpha (IFN-α) antiviral activity against HBV. IL-8 expression in serum was determined by enzyme linked immunosorbent assay (ELISA), and fluorescence-based quantitative real-time PCR (RT-qPCR) was used to measure IL-8 mRNA in peripheral blood mononuclear cells (PBMCs) in patients with CHB. IL-8 protein expression was detected in liver biopsy tissues by immunohistochemistry. In addition, the differences in serum IL-8 and PBMCs mRNA levels were also observed in patients with different anti-viral responses to IFN-α. Compared to normal controls, serum IL-8 protein and mRNA levels were increased in CHB patients, IL-8 levels were positively correlated with the severity of liver inflammation/fibrosis. Moreover, serum IL-8 protein and mRNA levels were positively correlated with serum alanine aminotransferase (ALT) level and negatively correlated with serum prealbumin (PA) level. IL-8 expression was mainly located in portal area of liver tissues and was increased with the severity of liver inflammation and fibrosis stage. The expression serum and mRNA levels of IL-8 in the CHB patients with a complete response to IFN-α are significantly lower than that of the patients with non-response to IFN-α treatment. It is suggested that IL-8 might play important roles in the pathogenesis of CHB. Moreover, interferon resistance may be related to the up-regulation of IL-8 expression in the patients did not respond to IFN-α treatment.
本研究的目的是分析慢性乙型肝炎（CHB）感染患者血清和肝组织中白细胞介素-8（IL-8）的表达水平，并研究IL-8是否可能拮抗干扰素-α（IFN-α）对乙肝病毒（HBV）的抗病毒活性。采用酶联免疫吸附测定（ELISA）法测定血清中IL-8的表达，运用基于荧光的定量实时聚合酶链反应（RT-qPCR）检测CHB患者外周血单个核细胞（PBMCs）中IL-8 mRNA。通过免疫组织化学检测肝活检组织中的IL-8蛋白表达。此外，还观察了对IFN-α有不同抗病毒反应的患者血清IL-8和PBMCs mRNA水平的差异。与正常对照组相比，CHB患者血清IL-8蛋白和mRNA水平升高，IL-8水平与肝脏炎症/纤维化的严重程度呈正相关。此外，血清IL-8蛋白和mRNA水平与血清丙氨酸氨基转移酶（ALT）水平呈正相关，与血清前白蛋白（PA）水平呈负相关。IL-8表达主要位于肝组织的门管区，并随着肝脏炎症和纤维化程度的加重而增加。对IFN-α完全应答的CHB患者血清和mRNA中IL-8的表达水平显著低于对IFN-α治疗无应答的患者。提示IL-8可能在CHB的发病机制中起重要作用。此外，干扰素抵抗可能与对IFN-α治疗无应答患者中IL-8表达上调有关。
