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慢性酒精摄入与小鼠对呼吸道合胞病毒肺部感染易感性增加及致病作用的关联

Association of chronic alcohol consumption and increased susceptibility to and pathogenic effects of pulmonary infection with respiratory syncytial virus in mice.

作者信息

Jerrells Thomas R, Pavlik Jacqueline A, DeVasure Jane, Vidlak Debbie, Costello Amy, Strachota Jennifer M, Wyatt Todd A

机构信息

Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, Nebraska 68198-6495, USA.

出版信息

Alcohol. 2007 Aug;41(5):357-69. doi: 10.1016/j.alcohol.2007.07.001.

Abstract

Chronic alcohol abuse by human beings has been shown to be associated with increased susceptibility to pulmonary infections and severity of inflammatory responses associated with pulmonary infection. On the basis of the higher likelihood of exposure to respiratory viruses, people who abuse alcohol would logically be susceptible to respiratory viral infections. To test this hypothesis, mice were provided alcohol in drinking water for 13-16 weeks with the Meadows-Cook protocol and infected intranasally with respiratory syncytial virus. At various times after infection, severity of infection was determined by evaluation of cellular and cytokine composition of bronchoalveolar lavage fluid (BALF) and histologic evaluation of inflammation. Infection was associated with neutrophil infiltration in both groups, but the proportion and number of neutrophils in BALF were significantly greater in the alcohol consumption group than in the control group. Concentrations of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 in BALF in the alcohol consumption group were increased. Interferon (IFN)-gamma concentrations were lower in the alcohol consumption group at later times of infection. Pulmonary inflammation was cleared by 3-5 days after infection in the control group. In contrast, pulmonary inflammation was evident in the alcohol consumption group after 7 days of infection, and some mice showed severe inflammation with hemorrhage and edema. IFN-alpha/beta was evident in BALF at low concentrations in the alcohol consumption group for several days after infection, and increased mRNA for IFN-alpha/beta was also evident in the alcohol consumption group. This was accompanied by the presence of virus in this group at these times of infection. Chronic alcohol consumption increased severity of pulmonary infection with a virus that naturally infects hosts by an aerosol route. Infection of mice that had consumed alcohol chronically was more severe in terms of increased proinflammatory cytokine production, inflammation, and a failure to clear the virus from the lungs.

摘要

已表明人类长期酗酒与肺部感染易感性增加以及肺部感染相关炎症反应的严重程度有关。基于接触呼吸道病毒的可能性更高,酗酒者在逻辑上易患呼吸道病毒感染。为了验证这一假设,按照梅多斯 - 库克方案给小鼠饮用含酒精的水13 - 16周,然后经鼻内感染呼吸道合胞病毒。在感染后的不同时间,通过评估支气管肺泡灌洗液(BALF)的细胞和细胞因子组成以及炎症的组织学评估来确定感染的严重程度。两组感染均伴有中性粒细胞浸润,但饮酒组BALF中中性粒细胞的比例和数量显著高于对照组。饮酒组BALF中肿瘤坏死因子 - α和单核细胞趋化蛋白 - 1的浓度升高。在感染后期,饮酒组的干扰素(IFN) - γ浓度较低。对照组在感染后3 - 5天肺部炎症消退。相比之下,饮酒组在感染7天后肺部炎症明显,一些小鼠出现伴有出血和水肿的严重炎症。感染后数天,饮酒组BALF中低浓度的IFN - α/β明显,饮酒组中IFN - α/β的mRNA水平也升高。在这些感染时间点,该组同时存在病毒。长期饮酒会增加经气溶胶途径自然感染宿主的病毒引起的肺部感染严重程度。就促炎细胞因子产生增加、炎症以及无法从肺部清除病毒而言,长期饮酒小鼠的感染更为严重。

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