Alcohol consumption has adverse effects on many aspects of the host defense system and in associated with an increased risk of pulmonary infection. Intestinal bacterial translocation is a process whereby microorganisms or bacterial products (such as lipopolysaccharide [LPS]) transgress the intestinal wall and migrate tot he mesenteric lymph nodes or the portal circulation. Bacterial translocation implies a breakdown of intestinal barrier function. Multiple derangements promote translocation, including physical disruption of the gut mucosa, overgrowth of intestinal bacterial flora, or impaired host immune defenses. If translocating bacteria or LPS cannot be effectively contained by and eliminated from the mesenteric lymph nodes, or if the organisms (or LPS) gain access to the portal circulation, they may stimulate hepatic release of cytokines (e.g., tumor necrosis factor [TNF]) into the systemic circulation. The lung is the organ immediately downstream from the liver, and pulmonary defenses against infection may be compromised under these circumstances. This proposal will assess the impact of alcohol ingestion on bacterial translocation and elucidate the consequences of alcohol-associated translocation on the defenses of the respiratory tract against infection. Our hypothesis is that bacterial translocation is facilitated by alcohol administration, which leads to downregulation of pulmonary defense mechanisms. We will test this hypothesis in a rat model of alcohol ingestion.
The specific aims of this proposal are: 1) To assess the effect of alcohol administration on the process of bacterial translocation. 2) To determine the effects of alcohol-associated bacterial translocation on pulmonary antibacterial mechanisms. An understanding of how alcohol affects bacterial translocation will facilitate preventive modalities which could lower risk for pneumonia in alcohol-consuming patients.
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