Is there a Place for Monoclonal Antibodies Against Endotoxin in the Therapy of Sepsis?
Sepsis remains the leading cause of mortality in critically ill patients. The naive belief that the introduction of new, more potent antibiotics will be sufficient to deal with the problem of infections has been discarded. Gram-negative sepsis is associated with a particularly high morbidity and mortality estimated between 20% and 75% [1–3]. Some characteristic features of gram-negative bacteria are believed to be reponsible for the not infrequent development of multiple organ failure and death despite the use of potent antibacterial compounds to sensitive microorganisms. The intravenous injection of endotoxin causing the typical clinical manifestations of gram-negative bacteremia including fever, shock-, leukopenia and/or leukocytosis and disseminated intravascular coagulation was revealed as far back as 1942 . Endotoxin has been proposed as a major causal factor in the development of gram-negative sepsis . Bacteremia and septic shock are associated with the release of endotoxin into the circulation which is believed to activate the biologic cascade involving tumor necrosis factor (TNF) and other cytokines such as interleukin-1 (IL-1) and interleukin-6 (IL-6). As the development of many systemic septic responses can be explained by the action of these substances, immunotherapy directed against endotoxin has been suggested as a possible method to decrease morbidity and mortality in patients with sepsis.
KeywordsSeptic Shock Adult Respiratory Distress Syndrome Federal Drug Administration Naive Belief Antiendotoxin Antibody
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