GRAM-NEGATIVE SEPSIS - PATHOPHYSIOLOGY OF INFECTION, DEVELOPMENT OF POLYCLONAL, MONOCLONAL HUMAN HYBRID AND MURINE ANTIENDOTOXIN ANTIBODIES

The mortality associated with sepsis of gram-negative etiology ranges from 5 to 50%, and can be as high as 90% in those patients who develop complications such as shock or organ failure. While a number of antimicrobial agents are active against the organisms most frequently associated with gram-negative sepsis, killing of the bacteria and the resultant release of endotoxin from the gram-negative bacterial cell wall may actually worsen the disease due to increased levels of toxins. Accordingly, agents capable of binding to and neutralizing endotoxin should prove to be a significant advance in the management of gram-negative sepsis. Polyclonal antibodies have been associated with variable results in human trials. In addition, it is unlikely that large supplies of reliable polyclonal anti-endotoxin antibodies will ever be available. Human hybrid (HA-1A) and murine (E5) anti-endotoxin have both been shown to provide significant protection against endotoxin and infections in experimental animal models of gram negative sepsis.