Septic shock is the most common cause of death of hospitalized children and adults. Bacterial toxins are the principal mediators that induce this highly lethal shock syndrome in patients. Endotoxin (a constituent of Gram negative bacteria has shown to produce a syndrome indistinguishable from bacterial septic shock in humans and animals. Thus, this important toxin is thought to be the major toxin involved in the pathogenesis of lethal septic shock in children and adults. Recently, in an important human study, immunization to gram-negative bacteria was effective in reducing mortality from septic shock. However, the mechanism of this protection was not clearly established from the study, and doubts about this treatment still exist. Thus, this treatment, despite being available for seven years, has not been accepted for clinical use. In the fall of 1988, we designed a controlled study, using the canine model, that would determine the efficacy of two specific anti-endotoxin antibodies (to endotoxin's core and side chain) as treatment for septic shock. Mechanism of action and efficacy could be determined form the hemodynamic measures, survival, and laboratory work (serial endotoxin levels, quantitative blood cultures, etc.) determined during the study. As of June 1991, all experiments are complete. The data are now being analysed and ancillary laboratory assays are being performed. Approximately four man years have been devoted to this project. This preclinical controlled trial (not possible in humans) will have direct implication for the future possible use of these antibodies to save human lives.
