Effects of recombinant bactericidal, permeability-increasing protein on bacterial translocation and pulmonary neutrophil sequestration in burned mice

Burn injury induces bacterial transloction (BT) from the gut in multiple animal models. Etiologic factors contributing to BT may be an ischemia-reperfusion injury to the gut, the release of inflammatory cytokines, oxygen metabolites and other mediators, and cytotoxic effects mediated by endotoxin (lipopolysaccharide). Bactericidal, permeability-increasing protein is a neutrophil granule protein with potent bactericidal and lipopolysaccharideneutralizing activities. The use of this protein has not been previously reported in a burninjury model. The purpose of this study was to determine whether recombinant bactericidal, permeability-increasing protein (rBPI23) affects the incidence of BT and myeloperoxidase content in lung tissue (a measure of leukocyte sequestration) in a burninjury model. Mice received a 32% total body surface area, full-thickness, scald burn, and 10 mg/kg body weight rBPI₂₃ in saline solution was given by intraperitoneal injection at 0, 3, and 6 hours after the burn. Control animals received intraperitoneal saline solution only. All animals received a total of 1 ml saline solution intraperitoneally immediately after burn injury for fluid resuscitation. At 24 hours after burn injury, mesenteric lymph nodes (MLN) were harvested, homogenized, and plated. Lung tissue was harvested and assayed for myeloperoxidase. Burned mice treated with rBPI₂₃ had a significantly (p=0.005, Fisher’s Exact Test, two-tailed) decreased incidence of BT, compared to burned mouse controls. Leukosequestration into lung tissues was not affected by rBPI₂₃. Postburn administration of rBPI₂₃ reduces but does not abolish the incidence of BT after burn injury in mice, perhaps by reducing intestinal injury during burn shock and the ischemia-reperfusion period by inhibiting the effects of lipopolysaccharide. An alternate explanation may be that rBPI₂₃ could increase clearance and lulling of bacteria by host defenses.