title: Response of man to endotoxin.
abstract: Endotoxin, a cell wall component of Gram-negative bacteria, plays a central role in the pathogenesis of septic shock. By administering small doses of intravenous endotoxin to humans, a variety of acute inflammatory responses are induced which are qualitatively similar to those that occur during the early stages of septic shock. Within hours of the administration of intravenous endotoxin to human volunteers, changes occur in systemic hemodynamics, ventricular function, pulmonary gas exchange and permeability. In conjunction with these changes in organ function, a wide variety of inflammatory mediators are released which appear to contribute to these responses. These include the release of proinflammatory cytokines (e.g. tumor necrosis factor-alpha, IL-1 beta, IL-6, IL-8), activation of the fibrinolytic system, kallikrein-kinin generation and phospholipase A2 release. Phagocytic leukocytes are primed for enhanced inflammatory responses following endotoxin administration. Counter-regulatory responses are initiated in parallel and may serve to limit some of the end-organ responses by the inflammatory mediators. This human model provides a unique opportunity to extend previous concepts of acute inflammation and to evaluate the earliest responses activated after exposure to an important bacterial component. Defining the pathways and responses initiated during acute human endotoxemia may allow a better understanding of host responses that are critical to the development of organ dysfunction and shock due to severe infections.
authors.affiliation: Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: G D
authors.initials: GD
authors.lastname: Martich
authors.forename: A J
authors.initials: AJ
authors.lastname: Boujoukos
authors.forename: A F
authors.initials: AF
authors.lastname: Suffredini
mesh_terms: D016207:Cytokines / Q000096:biosynthesis; D004731:Endotoxins / Q000008:administration & dosage*; D006090:Gram-Negative Bacteria; D006321:Heart; D006439:Hemodynamics; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007249:Inflammation / Q000209:etiology; D007275:Injections, Intravenous; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D012772:Shock, Septic / Q000209:etiology*; D014115:Toxemia / Q000209:etiology*
chemical_list: D016207:Cytokines; D004731:Endotoxins