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.
