FETAL ALCOHOL SYNDROME AND IMMUNE DEFICIENCY

胎儿酒精综合症和免疫缺陷

• 批准号: 3110515
• 负责人: NORMAN D REED
• 金额: $ 6.11万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3110515
• 关键词: B lymphocyte; T lymphocyte; alcohol dehydrogenase; alcoholic beverage consumption; alcoholism /alcohol abuse; aldehyde dehydrogenases; dosage; embryo /fetus drug adverse effect; ethanol; fetal alcohol syndrome; genetic disorder; genetic strain; humoral immunity; immunodeficiency; laboratory mouse; newborn animals; phagocytes

The long-term goal of this project is to determine if fetal exposure to ethanol leads to immune impairment, and if so, the nature and extent of the immune deficiency. The approach uses female mice fed a liquid diet containing ethanol at various doses. Offspring of these mothers will be compared to offspring of control (chow-fed, liquid diet-fed, and isocaloric control-fed) animals. Mice at various ages from late fetal to 8-week old will be subjected to a variety of in vitro and in vivo immunological tests to assess competence of T cells, B cells, natural killer cells and phagocytic cells. If immune defects are found, further experimentation will be done to pinpoint the critical period of fetal development and minimum dose for alcohol-induced damage. Another question to be addressed is whether severity of immune dysfunction correlates with "classical" fetal alcohol syndrome anomalies such as craniofacial and brain defects. Off spring of alcohol-fed mothers will be tested several weeks after birth as well as in the late fetal and neonatal period to determine how long-lasting immune deficiencies are. Mice of inbred strains which differ in activity of alcohol-metabolizing enzymes, will be used to study the role of genetics in susceptibility to immune deficiency caused by maternal alcoholism. If this study demonstrates a high incidence of immune deficiency as a result of maternal alcohol consumption, there are obvious health-related implications. This study should increase our over-all understanding of risk to the fetus from maternal alcoholism. In addition, a correlation between classical fetal alcohol syndrome features and immune deficiency in expermental animals might alert the medical community to the advisability of examining FAS patients for immune deficiency as well as other currently recognized health risks associated with the syndrome.

该项目的长期目标是确定胎儿暴露于 乙醇导致免疫损伤，如果是这样， 免疫缺陷 该方法使用雌性小鼠喂养含有乙醇的液体饮食， 各种剂量。 这些母亲的后代将被比作 对照（普通饲料喂养、液体饲料喂养和等热量对照喂养）动物。 将对从胎儿晚期到8周龄的不同年龄的小鼠进行一次实验。 各种体外和体内免疫学试验，以评估 T细胞、B细胞、自然杀伤细胞和吞噬细胞。 如果免疫 如果发现缺陷，将进行进一步的实验，以查明 胎儿发育的关键时期和酒精诱导的最小剂量 损害 另一个需要解决的问题是免疫系统的严重程度是否 功能障碍与“典型”胎儿酒精综合征异常相关 例如颅面和大脑缺陷。 酒精喂养的母亲的后代 将在出生后几周以及胎儿晚期进行测试， 新生儿期，以确定如何持久的免疫缺陷。 酒精代谢活性不同的近交系小鼠 酶，将用于研究遗传学在易感性中的作用， 母亲酗酒引起的免疫缺陷。 如果这项研究表明，免疫缺陷的发病率很高， 由于母亲饮酒，有明显的健康相关 影响 这项研究应该增加我们对 母亲酗酒对胎儿的风险。 此外，一种相关性 经典的胎儿酒精综合征特征和免疫缺陷之间的关系， 实验动物可能会提醒医学界注意 检查FAS患者的免疫缺陷以及其他目前 与该综合征相关的公认健康风险。