Anti-endotoxin monoclonal antibodies protect by enhancing bacterial and endotoxin clearance

In this study, we sought to determine the mechanism(s) by which a type-specific anti-lipopolysaccharide monoclonal antibody (an IgG directed against the O-antigen polysaccharide region of Salmonella minnesota lipopolysaccharide) and its F(ab')2 fragments protect during gram-negative bacterial peritonitis and endotoxemia in mice. During peritoneal infection, (1) IgG significantly decreased mortality, bacteremia, and endotoxemia at all time points compared with saline solution pretreatment and (2) F(ab')2 fragments reduced mortality at 24 hours but not thereafter, and had no effect on bacteremia but reduced endotoxemia compared with saline solution pretreatment. In the endotoxin model, IgG pretreatment significantly reduced mortality compared with saline solution pretreatment, while F(ab')2 fragments had no significant effect on mortality. No difference in endotoxemia was observed in mice that received IgG, F(ab')2 fragments, or saline solution pretreatment during endotoxemia. These results suggest that type-specific anti-lipopolysaccharide monoclonal antibodies protect by Fc-mediated clearance of both bacteria and endotoxin.