The long-term objective of the proposed research is to define the cellular mechanisms of impairments of immunity due to ethanol. Alcohol abuse is a major health problem in terms of the treatment of acute alcoholism and the long-term secondary effects, such as an increased susceptibility to pathogenic and opportunistic organisms. Increased susceptibility to cancer and autoimmune diseases is suspected also to be associated with alcoholism. It is likely that many of the sequelae of alcohol abuse result from alterations in the immune system resulting from ingestion of ethanol. In the proposed study the effect of ethanol administration on immunocompetence will be evaluated in an inbred mouse model system at the cellular level, and the ability of the animals to resist challenge with obligate intracellular pathogens also will be examined. Specifically these studies will provide direct evidence for ethanol-mediated alterations in the following areas of cellular immunity: a) production of lymphokines by stimulated T-cells including production of IL-2; b) production of receptors for IL-2 and utilization of IL-2; c) response of isolated T-cells to IL-1 in terms of IL-1 receptor binding and IL-2 receptor induction; d) lymphokine production and cellular interactions involved in primary and secondary antibody production to T- dependent antigens; e) host defense mechanisms that require functional T-cell capability. Emphasis has intentionally been placed on the effects of ethanol on cells exposed to ethanol and byproducts of ethanol metabolism in vivo since this represents a situation closer to human alcoholism and will allow the definition of direct and indirect effects of ethanol on the immune system. Emphasis has been placed also on predominantly T-cell-dependent host functions since the effects of alterations in these functions have broad applicability to many aspects of host defense mechanisms including infectious diseases, cancer, and autoimmune diseases.
Showing the most recent 10 out of 26 publications
