MODIFICATION OF SPECIFIC IMMUNE RESPONSES BY ALCOHOL

酒精对特异性免疫反应的改变

基本信息

批准号：
6371323
负责人：
CARL WALTENBAUGH
金额：
$ 29.11万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-04-01 至 2003-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6371323
关键词：
T lymphocyte alcoholic beverage consumption antibody formation antigen presenting cell cellular immunity cytokine developmental immunology ethanol glutathione helper T lymphocyte humoral immunity immunopharmacology immunoregulation immunotoxicity laboratory mouse

项目摘要

Excessive alcohol consumption is a major threat to human health. Normal host defense mechanisms are compromised in alcoholic patients, often resulting in pronounced frequency and severity of infections. Both clinical and experimental evidence suggest that alcohol alters the immune system. Chronic alcohol consumption impairs induction of human cell- mediated immune responses and elevates serum antibody levels. Studies from our laboratory during the initial granting period for this ongoing project, show that ethanol has a twofold effect on the immune response; it enhances specific humoral immunity and impairs induction of specific cell- mediated immunity. More specifically, ethanol enhances poly(Glu5OTyr50) (GT)-specific humoral immunity and impairs poly(Glu6OAla3OTyr10)(GAT)- specific cell-mediated immunity regulated by CD4-bearing helper (Th) lymphocytes designated Th2 and Th1, respectively. Despite the importance of alcohol in compromising host defense, little is known of the mechanism(s) underlying ethanol-caused immune alteration. New findings from our laboratory strongly suggest that ethanol alters cytokine expression, resulting in profound alteration of immune function. We propose that alteration of cytokine expression by ethanol plays a critical role in the modification of specific immune responses by alcohol consuming individuals. We propose to direct the activities of our laboratory toward three major goals: 1) To further define the conditions and the extent whereby ethanol alters the immune function in inbred strains of mice. 2) To determine which cells of the immune system are affected by ethanol consumption, and 3) To determine the underlying mechanism(s) for ethanol's alteration of specific immune function. Our laboratory is now in a position to critically assess how alcohol alters immune function. Our data suggest that one of the mechanisms whereby alcohol alters immune function is by the up- or downregulation of cytokine expression. These experiments are designed to critically evaluate whether alcohol or its metabolites affect cytokine expression in a manner that favors one type of immune function over another. These studies are critical to the development of therapeutic strategies for alcoholic patients who are a risk to infectious disease.

过度饮酒是对人类健康的主要威胁。普通的酒精患者通常会损害宿主防御机制导致感染的明显频率和严重程度。两个都临床和实验证据表明酒精会改变免疫系统。长期饮酒会损害人类细胞的诱导介导的免疫反应并提高血清抗体水平。研究我们的实验室在最初的授予期内项目表明乙醇对免疫反应有双重影响。它增强特定的体液免疫力并损害特定细胞的诱导介导的免疫力。更具体地，乙醇增强了聚（GLU5OTYR50）（GT） - 特异性的体液免疫和损害poly（Glu6oala3otyr10）（GAT） - 特异性细胞介导的免疫力由CD4固定辅助器调节（Th）淋巴细胞分别指定了TH2和TH1。尽管很重要妥协的宿主防御中的酒精，对乙醇引起的免疫改变的机制。新发现从我们的实验室强烈表明乙醇会改变细胞因子表达，导致免疫功能的深刻改变。我们提出乙醇对细胞因子表达的改变会发挥关键通过饮酒来修饰特定免疫反应的作用个人。我们建议将实验室的活动引向三个主要目标：1）进一步定义条件和程度乙醇在小鼠的近交菌株中的免疫功能改变。 2）确定免疫系统的哪些细胞受乙醇的影响和3）确定乙醇的基本机制特定免疫功能的改变。我们的实验室现在正在批判性评估酒精如何改变免疫功能的位置。我们的数据建议酒精改变免疫功能的机制之一是通过细胞因子表达的上调或下调。这些实验旨在批判性地评估酒精还是其代谢物是以有利于一种免疫的方式影响细胞因子表达另一个功能。这些研究对于发展至关重要酗酒患者的治疗策略，这些患者有传染性的风险疾病。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Fatty acid ethyl ester synthesis by the isolated perfused rat heart.

通过离体灌注大鼠心脏合成脂肪酸乙酯。

DOI：
10.1016/s0026-0495(97)90081-0
发表时间：
1997
期刊：
Metabolism: clinical and experimental
影响因子：
0
作者：
Chang,W;Waltenbaugh,C;Borensztajn,J
通讯作者：
Borensztajn,J

Phenotype of lymphocytes mediating copolymer-specific humoral immunity in ethanol-consuming C57BL/6 mice.

乙醇消耗的 C57BL/6 小鼠中淋巴细胞介导共聚物特异性体液免疫的表型。

DOI：
10.1016/0741-8329(94)90011-6
发表时间：
1994
期刊：
Alcohol (Fayetteville, N.Y.)
影响因子：
0
作者：
Waltenbaugh,C;Hsiung,L
通讯作者：
Hsiung,L

Differential effects of T-cell activation on gastric and small bowel permeability in alcohol-consuming mice.

T 细胞激活对饮酒小鼠胃和小肠通透性的不同影响。

DOI：
10.1097/01.alc.0000030620.75522.74
发表时间：
2002
期刊：
Alcoholism, clinical and experimental research.
影响因子：
0
作者：
Alnadjim,Ziad;Kayali,Zeid;Haddad,Wael;Holmes,EarlW;Keshavarzian,Ali;Mittal,Navdha;Ivancic,David;Koehler,Ronald;Goldsmith,David;Waltenbaugh,Carl;Barrett,TerrenceA
通讯作者：
Barrett,TerrenceA

Prolonged Hya-disparate skin graft survival in ethanol-consuming mice: correlation with impaired delayed hypersensitivity.

消耗乙醇的小鼠中 Hya 不同的皮肤移植物存活时间延长：与迟发型超敏反应受损的相关性。

DOI：
10.1097/00000374-200110000-00019
发表时间：
2001
期刊：
Alcoholism, clinical and experimental research
影响因子：
0
作者：
Wang,K;Busker-Mannie,AE;Hoeft,J;Vasquez,K;Miller,SD;Melvold,RW;Waltenbaugh,C
通讯作者：
Waltenbaugh,C