Effects of chronic alcohol consumption on pathogenesis of respiratory viral infec
Effects of chronic alcohol consumption on pathogenesis of respiratory viral infec
批准号:
7888583
负责人:
THOMAS R JERRELLS
金额:
$2.38万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-07-15 至 2010-10-31
关键词:
AddressAdultAlcohol abuseAlcohol consumptionAlcoholsAnimal ModelAnimalsAntibody FormationAntigensAntiviral AgentsApplications GrantsBacterial InfectionsBiological AssayCD4 Positive T LymphocytesCD8B1 geneCell surfaceCellsChronicChronic lung diseaseCommunicable DiseasesDataDevelopmentExploratory/Developmental GrantFailureHelper-Inducer T-LymphocyteHumanImmune responseInfectionInfection ControlInflammationInflammatoryInflammatory ResponseInterferon ReceptorInterferon Type IInterferonsInterventionLungLymphocyte ActivationMediator of activation proteinModelingNK Cell ActivationPathogenesisPathogenicityPneumoniaPredispositionProductionReceptor SignalingRespiratory Tract InfectionsRespiratory physiologyRespiratory syncytial virusSeveritiesSignal TransductionSuggestionT-LymphocyteTestingTimeTumor Necrosis Factor-alphaTumor Necrosis FactorsViralVirusVirus Diseasesalcohol effectbasechemokinechronic alcohol ingestioncytokinemigrationmouse modelrespiratoryresponse
中文摘要
描述
人类的酒精滥用和酒精消费的动物模型已经被证明与
先天性和获得性免疫反应受到抑制,这增加了对
感染的致病性。与酗酒有关的重要传染病包括
呼吸道感染几个小组已经研究了实验动物肺部的细菌感染,
动物,但很少有资料已获得关于慢性酒精消费的影响,
肺部病毒感染我们建立了慢性饮酒的动物模型,
肺部病毒感染我们获得的初步数据支持这样一种观点,
消费与感染的严重程度增加有关。提出了以下假设:
根据初步数据,并将在一个完善的慢性(月)酒精动物模型中进行测试
与人类肺部感染相关的病毒模型一起食用。
首要的假设是,慢性酒精滥用导致增加的易感性,
呼吸道病毒感染的严重程度。本文中提出的具体假设
探索性/发展性赠款申请如下:
1.慢性饮酒改变了对肺病毒的早期(先天)免疫反应
感染
A.通过抑制自然杀伤细胞的激活来限制病毒感染的早期控制,
干扰素(IFN)的产生。
B。增加促炎细胞因子和趋化因子的产生。持续的病毒感染
将导致这些介质的持续产生,导致持续的肺
炎症此外,不能通过IFN受体发出信号将限制对肿瘤的早期控制。
感染
2.长期饮酒抑制获得性免疫反应并偏向T辅助细胞
细胞亚型2(TH 2)限制抗原特异性CD 8 + T细胞迁移或活化(或两者)的型应答
细胞来清除肺部感染
这些作用的组合将抑制病毒感染的清除,并因此增加免疫应答。
肺部的炎症反应,以及可能增加发展的机会,
慢性肺部疾病,会损害肺功能。
从该探索性补助金申请中获得的数据将为进一步的机械RO 1提供基础
应用程序.最终,这项研究将产生关于酒精影响的重要信息。
滥用肺部病毒感染的致病性,也许还有潜在的干预措施。与酗酒有关的一种重要传染病是
呼吸道感染,但获得的信息很少
长期饮酒对肺部病毒感染的影响。
因为酒精会抑制免疫反应
滥用和酒精相关的肺部变化,这是合理的建议
增加呼吸道病毒感染的易感性。
英文摘要
DESCRIPTION
Alcohol abuse by human beings and animal models of alcohol consumption have been shown to be associated
with suppression of innate and acquired immune responses, which increases susceptibility to and
pathogenicity of infections. Among the more important infectious diseases associated with alcohol abuse are
respiratory infections. Several groups have investigated bacterial infections of the lungs of experimental
animals, but little information has been obtained regarding the effects of chronic alcohol consumption on
pulmonary viral infections. We have established an animal model of chronic alcohol consumption and
pulmonary viral infection. The preliminary data we have obtained support the suggestion that chronic alcohol
consumption is associated with increased severity of infection. The following hypotheses are proposed on the
basis of the preliminary data and will be tested in a well-established animal model of chronic (months) alcohol
consumption with a virus model relevant to pulmonary infections of human beings.
The overarching hypothesis is that chronic alcohol abuse results in increased susceptibility to and
severity of respiratory viral infections. Specific hypotheses addressed in this
exploratory/developmental grant application are the following:
1. Chronic alcohol consumption alters the early (innate) immune responses to a pulmonary viral
infection to
A. limit early control of viral infection by suppressing activation of natural killer cells, which limits
production of interferon (IFN)-¿.
B. increase production of proinflammatory cytokines and chemokines. The continued viral infection
would result in sustained production of these mediators, resulting in continued pulmonary
inflammation. Further, failure to signal through the IFN receptor would limit the early control of the
infection.
2. Chronic alcohol consumption suppresses the acquired immune response and biases to a T helper
cell subtype 2 (TH2)type response to limit migration or activation (or both) of antigen-specific CD8+ T
cells to clear infection in the lungs.
A combination of these effects would inhibit clearance of the viral infection and, thus, increase the
inflammatory response in the lungs, as well as possibly increase the chances of development of
chronic lung disease, which would impair lung function.
The data obtained from this exploratory grant application would provide the basis for a further mechanistic RO1
application. Ultimately, this line of study would yield important information regarding the effects of alcohol
abuse on the pathogenicity of pulmonary viral infections and, perhaps, potential interventions. One of the more important infectious diseases associated with alcohol abuse are
respiratory infections, but there have been little information obtained regarding
the effects of chronic alcohol consumption on pulmonary viral infections.
Because of the suppression of the immune response associated with alcohol
abuse and alcohol-associated changes in the lung, it is reasonable to suggest
increased susceptibility to respiratory viral infections.
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科研奖励(0)
会议论文
Effects of chronic alcohol consumption on pathogenesis of respiratory viral infec
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批准号:7660500
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项目类别:
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资助金额:$17.46万
-
财政年份:2008
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负责人:THOMAS R JERRELLS
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依托单位:
Effects of chronic alcohol consumption on pathogenesis of respiratory viral infec
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批准号:7534917
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项目类别:
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资助金额:$21.13万
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负责人:THOMAS R JERRELLS
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依托单位:
ROLE FOR VIRAL INFECTION IN ALCOHOLIC PANCREATITIS
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批准号:6681050
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项目类别:
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负责人:THOMAS R JERRELLS
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依托单位:
A ROLE FOR VIRAL INFECTION IN ALCOHOLIC PANCREATITIS
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负责人:THOMAS R JERRELLS
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依托单位:
A ROLE FOR VIRAL INFECTION IN ALCOHOLIC PANCREATITIS
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BIOCHEMISTRY AND IMMUNOLOGY OF ALCOHOLIC LIVER DISEASE
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海外基金