Bacterial infection is a frequent and serious problem in burn victims who survive the shock phase of thermal injury, due to the combination of impaired immunity and loss of the skin barrier to bacteria. Our work, plus the clinical studies of others, suggests that the gut can serve as a reservoir for systemic infections caused by bacteria that cross (translocate) the GI epithelium. Bacterial translocation from the GI tract does not normally occur in the healthy animal due to: a) the presence of an indigenous GI microflora preventing bacterial overgrowth, b) an intact intestinal epithelial barrier and c) normal host immune defenses. A thermal injury, either directly or indirectly can result in disruption or impairment of any of these protective mechanisms. The two aims of the investigation outlined in this proposal will be to: 1) to determine which mechanisms promote bacterial translocation from the gut after a thermal injury, and 2) develop immunologic strategies to prevent systemic infections by bacteria colonizing the patient's GI tract. Bacterial translocation will be measured by quantitatively culturing the mesenteric lymph node and various other organs of burned (30%) and unburned mice. To accomplish the first aim, five groups of experiments will be performed: 1) determine the translocation efficiencies of various microorganisms that commonly cause bacteremias in burn patients, 2) determine whether endotoxin from gram-negative enteric bacilli, in conjunction with a thermal injury, increases the permeability of the gut to translocating bacteria, 3) determine whether burn-induced gut ischemia, 4) starvation and protein malnutrition, or 5) products libertaed from the burn eschar promote bacterial translocation. In addition to the microbiologicap procedures, immunological and histological studies will be performed. To accomplish the second aim, the effect of various immunomodulators on bacterial translocation will be measured; including agents that stimulate neutrophil, lymphocyte, macrophage, and the RES activity. In the proposed project, the route of infection is a """"""""natural"""""""" oral route as compared with the artificial i.v. or i.p. routes often used to study infectious disease. Additionally, the bacteria translocating from the GI tract in our animal models are indigenous to the GI tract with natural ecological relationships to the host. The information generated will be of importance not only to physicians caring of the burn victim, but to physicians caring for severely immunocompromised patients who are at increased risk of developing nosocomial infection.
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