부산대학교 도서관

Septic processes due to the presence of bacteria or their products in body fluids are one of the mayor causes of death in ICU. We are working with two synthetic peptides (LBP8699 and LBPK95A), which correspond to the LPS-binding motif of human lipopolysaccharide binding protein (LBP) and a single-point mutant, respectively. We evaluated the same parameters in two animal models of different clinical relevance: a model of endotoxic shock, where mice received a lethal dose of Serratia marcescens LPS, and a model of infection, where mice were inoculated with Salmonella typhimurium ATCC 14028. In both models animals were treated with a unique dosage of the peptides. Levels of TNF-α were measured in blood (ELISA) and hepatic tissue (RT-PCR), 1 hour after challenge and both peptides indistinctly diminish the levels of this cytokine. TNF-α is one of the major fast-activated pro-inflammatory cytokines involved in the inflammatory cascade of sepsis. Their production is regulated by the activation of the nuclear factor kappa B (NFκB). The presence of significant amounts of LPS during Gram-negative infections induces cellular activation of NFκB. The induction of NFκB and the composition of the dimers were measured by electrophoretic mobility shift assay (EMSA) and super-shift assay, respectively using nuclear extracts of hepatic tissue in the model of endotoxic shock. Although dimeric composition was the same compared with control mice, the LBPK95A peptide diminished the expression of NFκB in the liver. This modulator effect in early stages of sepsis could be related with the improved survival observed in vivo in peptide-treated mice. [ABSTRACT FROM AUTHOR]