Influence of ethanol consumption on experimental viral hepatitis.
Influence of ethanol consumption on experimental viral hepatitis.
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乙醇消耗对实验性病毒性肝炎的影响。
DOI：
10.1097/01.alc.0000037138.62811.9e
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Hoerman,Debbie
中科院分区：
文献类型：
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作者：
Jerrells,ThomasR;Mitchell,Kristen;Pavlik,Jacqueline;Jerrells,Jennifer;Hoerman,Debbie
背景与酒精滥用相关的肝脏病理损害的一个重要因素是病毒性肝炎，尤其是丙型肝炎病毒(HCV)感染。饮酒已被证明与更严重的丙型肝炎病毒感染和肝炎有关。更严重的肝脏病毒感染的机制尚不清楚，由于缺乏嗜肝病毒感染的动物模型，研究一直受到阻碍。方法我们建立了一种小鼠病毒性肝炎模型系统，在该模型中，C57BL/6小鼠感染小鼠巨细胞病毒，这是一种在免疫能力强的小鼠中产生自限性肝炎的疱疹病毒。小鼠按配对喂养方案喂食含有36%酒精衍生卡路里的流食。在感染亚致死剂量的小鼠巨细胞病毒后，通过测定血清丙氨酸氨基转移酶水平和组织学评价来确定肝脏感染的严重程度。测定的其他指标包括血清细胞因子水平、肝脏样本中的细胞因子RNA水平和肝脏样本中的病毒浓度。结果与对照组相比，饲喂乙醇的小鼠在感染的后期阶段表现出更严重的肝炎。酒精喂养的小鼠不能控制肝脏中的病毒复制，这与更大的单核细胞炎症反应有关，单核细胞炎症反应主要由具有淋巴细胞和巨噬细胞形态特征的细胞组成。在酒精喂养的小鼠中，早期干扰素γ的产生以及整个感染过程中的产生明显较低。白介素12的早期产生在酒精喂养的小鼠中也较少。结论酒精喂养的小鼠出现更严重的肝炎可能是由于无法控制病毒的生长，这与持续的炎症反应有关。无法控制肝脏中的病毒可能与干扰素γ和白细胞介素12的产生减少有关。
BackgroundOne important contributor to pathologic effects on the liver associated with alcohol abuse is viral hepatitis, especially hepatitis C virus (HCV) infection. Alcohol consumption has been shown to be associated with more severe HCV infection and hepatitis. The mechanisms of the more severe viral infection of the liver are unclear, and studies have been hampered by the lack of an animal model of hepatotropic viral infections.MethodsWe have established a murine model system of viral hepatitis in which C57BL/6 mice are infected with murine cytomegalovirus, a herpesvirus that produces self‐limiting hepatitis in immunocompetent mice. Mice were fed a liquid diet containing 36% ethanol‐derived calories with a pair‐feeding protocol. After infection with a sublethal dose of murine cytomegalovirus, the severity of liver infection was determined by measuring serum levels of alanine aminotransferase and by histological evaluation. Other parameters determined included the serum levels of cytokines, cytokine RNA in liver samples, and viral concentration in liver samples.ResultsEthanol‐fed mice showed more severe hepatitis in the later stages of the infection as compared with the hepatitis noted in control mice. The ethanol‐fed mice did not control the virus replication in the liver, which was associated with a greater mononuclear cell inflammatory response, composed predominantly of cells with morphological characteristics of lymphocytes and macrophages. The early production of interferon γ, as well as production throughout the infection, was significantly lower in the ethanol‐fed mice. The early production of interleukin 12 was also less in ethanol‐fed mice.ConclusionsThe more severe hepatitis seen in the ethanol‐fed mice is likely to be the result of an inability to control the growth of the virus, which is associated with a continued inflammatory response. The inability to control the virus in the liver may be related to the decreased production of interferon γ and interleukin 12.