Acute ethanol ingestion commonly contributes to the etiology of burn injuries as nearly 50% of severe burns occurs in association with ethanol consumption. Excessive ethanol consumption is closely linked with trauma-related hospital admissions, especially in young adults and working-age individuals and contributes to increased length of hospital stays and mortality after burn trauma. This increased mortality is largely due to severe sepsis.  Previous studies have shown that disruption of the intestinal endothelium is a primary mechanism that results in lethal sepsis and multiple organ failure. Increased postburn endothelial permeability associated with deranged neutrophil activity are likely mechanisms that together modulate the postburn intestinal inflammatory response. As such, we will investigate the degree to which burn injury alone and burn injury combined with acute ethanol exposure affects postburn plasma extravasation, myeloperoxidase levels, and the production of pro-inflammatory cytokines and chemokines in the ileum. In addition, the protein levels and cellular localization of the tachykinin, Substance P, a known neutrophil chemoattractant, will be assayed in the ileum. Substance P is known to modulate the function of immunocompotent and inflammatory cells and enhances production of pro-inflammatory mediators such as cytokines and cell surface receptors.  Importantly, acute ethanol exposure produces a dose-dependent nerve fiber release of Substance P in intestinal tissue. Based on the cellular changes present within the small intestines, we propose a neuropeptide-related  mechanism for augmentation of neutrophil infiltration observed in murine burn injury combined with acute ethanol exposure when compared with murine burn injury alone.