ABSTRACT

III. ADMINISTRATION OF ENDOTOXIN TO AND MEASUREMENT OF ENDOTOXEMIA IN HUMANS AND ANIMALS: INVESTIGATING THE ROLE OF ENDOTOXIN AS A POTENTIAL THERAPEUTIC TARGET IN SEPTIC SHOCK 595 A. Data Supporting Endotoxin as an Important Toxin in Septic Shock 595 B. Data Not Supporting Endotoxin as an Important Therapeutic

Target in Septic Shock 596

IV. STUDIES USING ENDOTOXIN AS A THERAPEUTIC TARGET IN EXPERIMENTAL AND CLINICAL SEPTIC SHOCK 597 A. Endotoxin Antibodies Directed at the 0-Side Chain 598 B. Polyclonal Antibodies Directed at the Endotoxin Core and Lipid A 599 C. Monoclonal Antibodies Directed Against the Endotoxin Core and

Lipid A 601

V. NONANTIBODY THERAPIES DIRECTED AT ENDOTOXIN IN SEPTIC SHOCK A. Nonantibody Agents That Bind Endotoxin B. Analogues of Lipid A C. Plasma Detoxification

VI. CONCLUSION

REFERENCES

604 604 605 606

I. INTRODUCTION

Over the past 50 years, researchers have used purified endotoxin in animals and human volunteers to study the pathophysiology of septic shock. During this time, scientists have speculated about the role of endotoxin in producing human septic shock. Some believed that endotoxin was the agent that could induce all forms of shock (Fine, 1954; Ravin et al., 1960; van Deventer et al., 1988). Others were convinced that endotoxin was only one of several mediators that could cause the septic syndrome (Zweifach et al., 1958; Danner et al., 1989a).