Intrahepatic cytokine expression is downregulated during HCV/HIV co-infection
Intrahepatic cytokine expression is downregulated during HCV/HIV co-infection
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DOI：
10.1002/jmv.20528
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发表时间：
2006-02-01
影响因子：
12.7
通讯作者：
Chung, RT
中科院分区：
文献类型：
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作者：
Blackard, JT;Komurian-Pradel, F;Chung, RT
HIV合并感染与HCV治疗应答率降低和HCV相关肝病加速相关。细胞因子在慢性HCV感染期间调节肝脏炎症和纤维化中起重要作用，但HIV和/或其治疗对细胞因子表达的作用尚不清楚。从12名HCV单感染者和14名HCV/HIV共感染者的肝活检组织中提取总RNA。我们使用实时PCR来定量有助于先天性和适应性免疫应答的细胞因子，包括IFN α，IFN γ、TNF α、TGF β（1）、IL-2、IL-4、IL-8、IL-10和IL-12 p40。使用分子信标方法定量正链和负链HCV RNA水平。两组阳性链HCVRNA检出率均为100%;在4例（33%）HCV单感染者和9例（64%）HCV/HIV合并感染者中检出了阴性链HCVRNA。两组之间的中位链特异性HCV RNA水平没有显着差异。与HCV单一感染组相比，HCV/HIV合并感染组的细胞因子mRNA检出率较低; TNF α、IL-8和IL-10的检出率具有统计学意义。总体而言，HCV/HIV共感染者的细胞因子mRNA量低于HCV单感染者，但TGF β除外（1）。这些数据表明，在细胞因子激活的缺陷可能会发生在HCV/HIV合并感染的人，限制了HCV从肝脏的有效清除。
HIV co-infection is associated with reduced HCV treatment response rates and accelerated HCV-related liver disease. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the roles of HIV and/or its therapies on cytokine expression are unknown. Total RNA was extracted from liver biopsies of 12 HCV monoinfected and 14 HCV/HIV co-infected persons. We used real-time PCR to quantify cytokines that contribute to innate and adaptive immune responses, including IFN alpha., IFN gamma, TNF alpha, TGF beta(1), IL-2, IL-4, IL-8, IL-10, and IL-12p40. Positive- and negative-strand HCV RNA levels were quantified using a molecular beacon approach. Detection of positive-strand HCV RNA was 100% in both groups; negative-strand HCV RNA was detected in four (33%) HCV mono-infected persons and in nine (64%) HCV/HIV co-infected persons. Median strand-specific HCV RNA levels were not significantly different between the two groups. Detection rates of cytokine mRNAs were lower for the HCV/HIV co-infected group compared to the HCV mono-infected group; the detection rates for TNF alpha, IL-8, and IL-10 were statistically significant. Overall, cytokine mRNA quantities were lower for HCV/HIV co-infected compared to HCV monoinfected persons, with the exception of TGF beta(1). These data suggest that a defect in cytokine activation may occur in HCV/HIV co-infected persons that limits efficient clearance of HCV from the liver.