A murine model for studying endotoxemia and the efficacy of anti-LPS agents in an immunocompromised host

Abstract

In most murine models of endotoxemia, an exogenous agent is injected to increase the sensitivity of the mouse to endotoxin (lipopolysaccharide, LPS). Here, a clinically encountered event, a bum, was found to reproducibly decrease the amount of LPS required to kill half of the mice (LD50). In this more clinically relevant model, the anti-LPS agents, monophosphoryl lipid A and polymyxin B sulfate, each increased the LD50 of burned mice challenged with LPS from Klebsiella pneumoniae, while the LPS-directed monoclonal antibody E5 did not. However, E5 did protect burned mice challenged with smooth or rough LPS from Salmonella typhimurium and S. minnesota, respectively. Hence, in vivo protection was dependent upon both the anti-LPS agent and the chemical composition of the LPS used for intoxication. The differences in protection observed in this intoxication model may explain some protection discrepancies reported when these anti-LPS agents have been tested for protection against Gram negative sepsis.