title: Endotoxin administration to humans primes alveolar macrophages for increased production of inflammatory mediators.
abstract: To elucidate potential mechanisms of the acute lung injury associated with endotoxemia, we evaluated the effect of intravenously administered endotoxin on the ability of alveolar macrophages isolated by bronchoalveolar lavage from normal subjects to produce inflammatory mediators. Within 1 hr of endotoxin (4 ng/kg body weight) administration, all 12 study subjects developed constitutional symptoms and leukopenia, and within 3 hr, low-grade fever. Resolution of symptoms and fever by 6 hr was accompanied by systemic granulocytosis. Although intravenously administered endotoxin appeared to activate a subset of circulating monocytes, it did not alter the bronchoalveolar lavage cell number, phenotype (95% macrophages), or constitutively expressed high levels of surface HLA-DR and O2-. In contrast, intravenous endotoxin primed the alveolar macrophages for enhanced lipopolysaccharide-induced secretion of interleukin-1 (11.8 to 25.8 U/ml; P = 0.04), tumor necrosis factor-alpha (titer, 6.8 to 13.6; P = 0.20), and prostaglandin E2 (38.4 to 116.3 ng/ml; P = 0.035). These results demonstrate that low-dose intravenous endotoxin primes human alveolar macrophages, which are already differentiated in situ, for enhanced secretion of inflammatory mediators. Such mediators may contribute to the pulmonary changes associated with endotoxemia and acute lung injury.
authors.affiliation: Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: P D
authors.initials: PD
authors.lastname: Smith
authors.forename: A F
authors.initials: AF
authors.lastname: Suffredini
authors.forename: J B
authors.initials: JB
authors.lastname: Allen
authors.forename: L M
authors.initials: LM
authors.lastname: Wahl
authors.forename: J E
authors.initials: JE
authors.lastname: Parrillo
authors.forename: S M
authors.initials: SM
authors.lastname: Wahl
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D004731:Endotoxins / Q000008:administration & dosage*; D004926:Escherichia coli; D005260:Female; D005334:Fever / Q000139:chemically induced; D005455:Fluorescent Antibody Technique; D006801:Humans; D007275:Injections, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008070:Lipopolysaccharides / Q000008:administration & dosage; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D013481:Superoxides / Q000378:metabolism
chemical_list: D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D013481:Superoxides; C044101:endotoxin, Escherichia coli; D015232:Dinoprostone