Alcohol-induced IgE Responses

酒精诱导的 IgE 反应

• 批准号: 7058861
• 负责人: CARL WALTENBAUGH
• 金额: $ 13.36万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-15 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7058861
• 关键词: B lymphocyte; alcoholic beverage consumption; cytokine; ethanol; helper T lymphocyte; immune response; immunoglobulin E; laboratory mouse

DESCRIPTION (provided by applicant): Immune response in alcoholics are compromised often putting these individuals at risk for frequent and severe infections. In both humans and mice different subsets of CD4 T helper cells, termed Th1 and Th2, regulate cell-mediated and antibody-mediated immunity, respectively. We previously demonstrated, in a mouse model that closely parallels immune alterations seen in humans, that ethanol consumption polarizes adaptive immune responses, Th1 responses are inhibited and Th2 responses are unaffected or enhanced. We recently made the startling preliminary observation that ethanol consumption (within 6-8 days) significantly increases serum IgE levels in unimmunized mice. In contrast, specific immunization regimens in non-alcohol consuming mice often require several weeks to obtain significant IgE levels. It is the robustness of this most polarized Th2 responses that affords us the opportunity to investigate the role of alcohol on Th2 mechanisms. The rapidity of increase in Serum IgE levels suggests that ethanol may rapidly up-regulate Th2 cytokines to stimulate B cells. The central hypothesis of the present exploratory/developmental proposal is that ethanol consumption promotes IgE responses through a Th2 cytokine burst. Three specific aims are proposed: 1) to determine whether Th2 cytokine/receptors are up-regulated, 2) to determine whether elevated IgE responses result from up-regulation of Th2 or down-regulation of Th1 cytokines, and 3) to determine the B cell source of IgE in alcohol-consuming mice. The experiments described represent an R21 exploratory/developmental proposal over a three-year time span. The proposed experiments are designed to help understand the underlying mechanisms of this most abused drug, alcohol, in polarizing the immune response toward Th2 function.

描述（由申请人提供）：酗酒中的免疫反应经常使这些人处于经常和严重感染的风险。在人类和小鼠中，CD4 T辅助细胞的不同亚群（称为Th1和Th2）分别调节细胞介导的和抗体介导的免疫。我们以前在人类中看到的与免疫改变相似的小鼠模型中，我们证明了乙醇的消耗量使适应性免疫反应偏振，Th1反应受到抑制，TH2反应不受影响或增强。最近，我们提出了令人震惊的初步观察，即乙醇消耗（在6-8天内）显着提高了非免疫小鼠的血清IgE水平。相反，非酒精饮用小鼠中的特定免疫方案通常需要几周才能获得显着的IgE水平。正是这种两极分化的TH2反应的鲁棒性使我们有机会研究酒精对TH2机制的作用。血清IgE水平增加的迅速性表明乙醇可能会迅速上调Th2细胞因子以刺激B细胞。本探索性/发育建议的中心假设是，乙醇消耗通过Th2细胞因子爆发来促进IgE反应。提出了三个具体目的：1）确定Th2细胞因子/受体是否被上调，2）确定IgE反应升高是由Th2上调或Th1细胞因子下调而导致的，而3）以确定饮酒小鼠中IgE的B细胞来源。描述的实验代表了三年时间内的R21探索性/发育建议。所提出的实验旨在帮助了解这种滥用药物的基本机制，即酒精，使对Th2功能的免疫反应极化。