Endotoxin, a product of gram-negative bacteria, is considered to be an important toxin in the development of septic shock. Lipid X, a monosaccharide precursor in the biosynthetic pathway of lipid A (the toxic component of endotoxin), has been shown in vitro to block some of the cellular effects of endotoxin in a manner consistent with competitive inhibition. Further, lipid X has been shown to protect mice and sheep from lethal challenge with endotoxin. In this investigation, the therapeutic efficacy of lipid X is being evaluated in a well characterized canine model of septic shock which utilized live bacteria implanted into an intraperitoneal clot. Demonstration of protective activity in an animal model using an actual infection with live gram-negative bacteria is necessary to assess the potential value of these novel agents in the treatment of septic shock. This project is nearly complete (the drug was not found to have therapeutic efficacy) and a manuscript is in preparation.
