Effect of recombinant bactericidal/permeability-increasing protein on endotoxin translocation and lipopolysaccharide-binding protein/CD14 expression in rats after thermal injury

Objective: To investigate the potential mechanisms underlying the in vivo e ffect of recombinant bactericidal/permeability-increasing protein (rBPI(21) ) on endogenous bacteria or endotoxin translocation and lipopolysaccharide- binding protein/CD14 expression secondary to thermal injury. Design: Prospective, randomized, controlled animal study. Setting: College hospital animal research laboratory. Subjects: Thirty-six male Wistar rats weighing 250-300 g. Interventions: The rats were anesthetized, and a 35% total body surface are a full-thickness burn was created. Animals were randomized to receive treat ment with either rBPI(21) or the control protein (albumin). rBPI(21) (2 mg/ kg body wt, BPI group) or a protein control preparation (burn group) in the same dose was administered in an intravenous bolus at 30 mins and 4 hrs af ter thermal injury. All animals were killed at 12 and 24 hrs postburn (six to ten rats for each interval). In addition, eight rats were taken as norma l controls. Measurement and Main Results: Our data showed that treatment with rBPI(21) was effective in preventing endotoxin translocation secondary to severe bur ns. Meanwhile, tissue lipopolysaccharide-binding protein, CD14, and tumor n ecrosis factor-alpha mRNA expression in various organs were inhibited marke dly by rBPI(21) secondary to acute insults (p < .05-.01). Furthermore, sign ificant reduction in serum aminoleucine transferase concentrations and elev ation in intestinal diamine oxidase activities in the rBPI(21)-treated grou p were found compared with controls (p < .05-.01). Conclusions: These findings indicate that endotoxin accumulated in local si tes after thermal injury can markedly up-regulate lipopolysaccharide-bindin g protein/CD14 and tumor necrosis factor-alpha mRNA expression in various o rgans. Meanwhile, up-regulation of lipopolysaccharide-binding protein/CD14 expression would be the major molecular mechanism of increasing sensitivity to endogenous endotoxin response after burns. Early treatment with rBPI(21 ) may be effective in attenuating multiple organ damage resulting from gut- origin endotoxin translocation. This might be associated with the down-regu lation effects of tissue lipopolysaccharide-binding protein and CD14 gene e xpression by the use of rBPI(21).