MECHANISM OF ETHANOL INDUCED IMPAIRMENTS IN IMMUNITY

乙醇引起免疫损伤的机制

基本信息

批准号：
6509163
负责人：
THOMAS R JERRELLS
金额：
$ 17.84万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-09-01 至 2004-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6509163
关键词：
adrenalectomy alcoholic beverage consumption alcoholism /alcohol abuse bactericidal immunity cellular immunity corticosteroids disease /disorder proneness /risk ethanol hormone regulation /control mechanism hypothalamic pituitary adrenal axis immunopharmacology immunosuppression laboratory mouse laboratory rat nutrition related tag pathogenic diet

项目摘要

DESCRIPTION: (Adapted from the Investigator's Abstract) Study results from my laboratory and reported by other researchers have shown that ethanol (ETOH) consumption by experimental animals and human beings is associated with an increased susceptibility to infectious diseases. Overall, this is associated mostly with defects in the generation of cell-mediated immune responses and the effector functions of lymphoid cells, including T and natural killer cells as well as macrophages. We and others have shown that ETOH consumption is also associated with activation of the hypothalamic-pituitary- adrenal (HPA) axis and that many of the changes in lymphoid cell numbers and function can be attributed to the resulting corticosteroids produced as a result of this activation. The general hypothesis to be tested in the studies proposed in this application is that the corticosteroids produced by ETOH-fed animals suppress innate and acquired immune responses that are necessary for host defenses against infectious microorganisms. This hypothesis and other more specific hypotheses resulting from the general hypothesis will be tested by using a murine model of ETOH consumption in a liquid diet with a pair-feeding paradigm. With the use of adrenalectomized mice we will determine whether immune responses to model T-cell-dependent antigens such as phosphocholine conjugated to key hole limpet hemocyananin or infectious microorganisms, including Listeria monocytogenes, Salmonella typhimurium, Nippostrongylus brasiliensis, and murine cytomegalovirus, are decreased by corticosteroids produced as a result of ETOH consumption. With this approach the role of ETOH-associated corticosteroid production on the cellular effectors of immunity, including natural killer cells, CD4+ and CD8+T cells, and macrophages will be tested. By using the various infectious model systems in place in this laboratory the ETOH-mediated effects on the subsets of helper T cells (TH-1 and TH-2) will also be defined.

描述：（改编自研究者的摘要）研究结果来自我的实验室和其他研究人员的报告表明，乙醇 (ETOH) 实验动物和人类的消耗是相关的对传染病的易感性增加。总的来说，这是主要与细胞介导的免疫产生缺陷有关淋巴细胞的反应和效应功能，包括 T 和自然杀伤细胞以及巨噬细胞。我们和其他人已经证明乙醇消耗也与激活下丘脑-垂体-肾上腺 (HPA) 轴以及许多变化淋巴细胞的数量和功能可归因于所产生的由于这种激活而产生的皮质类固醇。将军本申请提出的研究中要检验的假设是喂食 ETOH 的动物产生的皮质类固醇会抑制先天和获得性免疫反应是宿主防御所必需的传染性微生物。这个假设和其他更具体的假设由一般假设得出的假设将通过使用配对喂养流质饮食中 ETOH 消耗的小鼠模型范例。通过使用肾上腺切除的小鼠，我们将确定是否对模型 T 细胞依赖性抗原（例如磷酸胆碱）的免疫反应与匙孔血蓝蛋白或传染性微生物缀合，包括单增李斯特菌、鼠伤寒沙门氏菌、尼波圆线虫皮质类固醇可减少巴西利亚和鼠巨细胞病毒的感染由于乙醇消耗而产生。通过这种方法的作用细胞效应器上 ETOH 相关皮质类固醇的产生免疫，包括自然杀伤细胞、CD4+ 和 CD8+T 细胞，以及将测试巨噬细胞。通过使用各种感染模型系统在这个实验室中，ETOH 介导的对子集的影响辅助性 T 细胞（TH-1 和 TH-2）也将被定义。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Alterations in interleukin-2 utilization by T-cells from rats treated with an ethanol-containing diet.

用含乙醇饮食处理的大鼠 T 细胞对白细胞介素 2 利用率的改变。

DOI：
10.1111/j.1530-0277.1990.tb00480.x
发表时间：
1990
期刊：
Alcoholism, clinical and experimental research
影响因子：
0
作者：
Jerrells,TR;Perritt,D;Eckardt,MJ;Marietta,C
通讯作者：
Marietta,C

Ethanol ingestion increases susceptibility of mice to Listeria monocytogenes.

DOI：
10.1111/j.1530-0277.1993.tb00729.x
发表时间：
1993-02
期刊：
Alcoholism, clinical and experimental research
影响因子：
0
作者：
Assad Joe Saad;Rana Domiati-Saad;T. Jerrells
通讯作者：
Assad Joe Saad;Rana Domiati-Saad;T. Jerrells

Rescue of in vivo FAS-induced apoptosis of hepatocytes by corticosteroids either associated with alcohol consumption by mice or provided exogenously.

DOI：
10.1016/j.intimp.2004.09.035
发表时间：
2005-02
期刊：
International immunopharmacology
影响因子：
5.6
作者：
Laura Sosa;Debbie Vidlak;Jennifer M Strachota;Jacqueline A. Pavlik;T. Jerrells
通讯作者：
Laura Sosa;Debbie Vidlak;Jennifer M Strachota;Jacqueline A. Pavlik;T. Jerrells

Alcohol consumption by C57BL/6 mice is associated with depletion of lymphoid cells from the gut-associated lymphoid tissues and altered resistance to oral infections with Salmonella typhimurium.