Tissue lipopolysaccharide-binding protein expression in rats after thermal injury: potential role of TNF-α

Abstract

Recent studies have suggested that levels of lipopolysaccharide-binding protein (LBP) might play a harmful role by up-regulating the host’s sensitivity to endotoxin. Our previous studies demonstrated that local endotoxin could up-regulate LBP expression after acute insults, however, the definite molecular mechanisms downstream of endotoxin action remain unclear. This study investigates whether tumor necrosis factor (TNF-α) might be responsible for the LBP formation during endogenous endotoxemia postburn. Wistar rats were anesthetized, and a 35% TBSA full-thickness burn was created. Animals were randomly divided into normal control, thermal injury and anti-TNF-α mAb treatment group. A significant elevation of plasma endotoxin concentration was observed after acute insults. TNF-α levels in plasma also rapidly increased after thermal injury. Meanwhile, LBP mRNA expression markedly increased in liver, lungs, kidneys and intestine postburn. There was no detectable TNF-α in the plasma of anti-TNF-α mAb treated animals. Treatment with anti-TNF-α mAb also resulted in significantly lower concentrations of LBP mRNA in local tissues. Additionally, several organ function parameter levels in plasma significantly decreased in treatment group. These results demonstrated that an increase of plasma TNF-α levels caused by burns might be associated with a marked elevation of tissue LBP mRNA expression, which could contribute to the development of multiple organ damage.