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Development and potential use of antibody directed against lipopolysaccharide for the treatment of gram-negative bacterial sepsis.

Gram-negative bacterial sepsis remains a major cause of lethality in hospitalized patients, despite routine therapy consisting of antimicrobial agents, hemodynamic monitoring and fluid resuscitation, and metabolic support. Because a large body of evidence supports the concept that Gram-negative bacterial lipopolysaccharide (endotoxin, LPS) is responsible for many of the direct and host mediator-induced deleterious effects, recent work has been centered on the development and use of anti-LPS antibody preparations in order to ameliorate lethality. Both polyclonal and monoclonal antibody preparations directed against the common deep core/lipid A region of LPS are cross-reactive in vitro and cross-protective in vivo against a wide range of challenge organisms and LPS, and preliminary clinical trials indicate that a reduction in lethality may be possible. The precise endotoxin epitope against which antibody should be directed in order to maximize protection, however, has not been established. This modality most probably will become a standard form of adjunctive therapy within the next several years for the treatment of Gram-negative bacterial sepsis.