Mechanisms of Endotoxin Tolerance and their Effectiveness during the Febrile Phase of Gram-Negative Bacterial Infections in Man
Understanding the role of endotoxin in the pathogenesis of human gram-negative bacterial infection requires the elucidation of the mechanisms by which man develops resistance to this toxin. In contrast to animal models, few critical studies are available concerning human mechanisms of tolerance acquisition to endotoxin. Even fewer studies are available concerning the effectiveness of these tolerance mechanisms during the febrile phase of gram-negative bacterial illness. This report reviews the tolerant responses of man to bacterial endotoxin as assessed by febrile and subjective toxic reactivity. Our experience is based upon studies in several hundred volunteers, both healthy and overtly ill with gram-negative bacterial infections (typhoid fever or tularemia), given repetitive intravenous injections of bacterial endotoxins from various sources. These studies were conducted for the primary purpose of developing improved prophylactic and therapeutic approaches to gram-negative bacterial infection. All volunteers were fully informed of the nature of these studies and were free to withdraw at any time. Where pertinent, results of animal studies are included to supplement the human data.
KeywordsKupffer Cell Typhoid Fever Tolerance Mechanism Bacterial Endotoxin Refractory State
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