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被证明是相关的
通过抑制先天和后天免疫反应,增加了对和
感染的致病性。与酗酒有关的更重要的传染病包括
呼吸道感染。几个小组已经调查了实验性肺炎的肺部细菌感染
动物,但关于长期饮酒对健康的影响的信息很少
肺部病毒感染。我们已经建立了一个慢性酒精消费的动物模型,
肺部病毒感染。我们获得的初步数据支持长期饮酒的说法
消费与感染严重程度的增加有关。提出了以下假设:
在初步数据的基础上,将在已建立的慢性(数月)酒精动物模型中进行测试
与人类肺部感染有关的病毒模型的消费。
最重要的假设是,长期酗酒会增加患酒精症的易感性
呼吸道病毒感染的严重程度。在这篇文章中提出的具体假设
试探性/发展性赠款申请如下:
1.长期饮酒改变了对肺部病毒的早期(先天)免疫反应
感染到
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,这限制了
干扰素(干扰素)的生产。
B.增加促炎细胞因子和趋化因子的产生。持续的病毒感染
会导致这些介质的持续产生,从而导致持续的肺
发炎。此外,如果不能通过干扰素受体发出信号,将限制对
感染。
2.长期饮酒会抑制获得性免疫反应,并偏向T辅助
限制抗原特异性CD8 T迁移或激活(或两者兼有)的细胞亚型2(TH2)型反应
清除肺部感染的细胞。
这些影响的组合将抑制病毒感染的清除,从而增加
在肺部的炎症反应,以及可能增加发展的机会
慢性肺病,会损害肺功能。
从这一探索性拨款申请中获得的数据将为进一步的机械性RO1提供基础
申请。最终,这一系列研究将提供有关酒精影响的重要信息。
滥用肺部病毒感染的致病性,或许还有潜在的干预措施。与酗酒有关的一种更重要的传染病是
呼吸道感染,但几乎没有获得关于
慢性饮酒对肺部病毒感染的影响
因为与酒精相关的免疫反应受到抑制
滥用和酒精相关的肺部变化,有理由建议
对呼吸道病毒感染的易感性增加。
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.
期刊论文(0)
专著(0)
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
-
项目类别:
-
资助金额:$17.46万
-
财政年份:2008
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负责人:THOMAS R JERRELLS
-
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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财政年份:2008
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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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资助金额:$14.23万
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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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批准号:6923628
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项目类别:
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资助金额:$14.7万
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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