Alcohol abuse is the single largest environmental factor associated with health problems in the US. Prolonged and excessive consumption of ethanol lowers many aspects of host defenses, resulting in an increased susceptibility to infection. However, no studies to date have assessed the mechanism(s) by which chronic alcohol exposure comprises immune function. A number of endocrine hormones and neuromodulators, including glucocorticoids, endogenous opiates and eicosanoids, are known to modulate immune function either by acting directly on lymphocytes or through mediators such as lymphokines. The synthesis and the secretory patterns of these substances are altered by chronic exposure to alcohol in adulthood and by exposure to ethanol in utero, thus alcohol exposure-induced perturbations in immunocompetence may result in part from a disruption of normal endocrine homeostasis. This proposal is designed to use a rat model to study the influence of chronic alcohol exposure, with or without exposure to ethanol in utero, on immune function and the involvement of hormones as possible mediators of alcohol-induced changes in immunocompetence. Overall, these studies are designed to determine: 1) The duration of chronic exposure to alcohol necessary in this rat model to comprise immune functions, such as specific and non-specific antigen responses, antibody production and delayed-type hypersensitivity, and how long such a suppression may last following cessation of alcohol administration. 2) Whether fetal alcohol exposed (FAE) offspring exhibit an enhanced endocrine responsiveness and susceptibility to immune suppression by chronic alcohol exposure in adulthood. 3) The contribution of specific hormones, glucocorticoids, endogenous opiates and eicosanoids, as mediators of alterations in immunocompetence induced by chronic alcohol exposure, with or without FAE, by manipulating the hormonal state of the animal prior to and during chronic ethanol exposure.
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