title: Transcompartmental inflammatory responses in humans: IV versus endobronchial administration of endotoxin*.
abstract: OBJECTIVE
  Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following lipopolysaccharide-induced pulmonary and systemic inflammation.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, crossover study.
  Healthy male volunteers.
  
  
  METHODS
  Fifteen volunteers (mean age, 23; SD, 2 yr) received Escherichia coli endotoxin (lipopolysaccharide, 4 ng/kg) IV or endobronchially on two different study days. Groups were evaluated by bronchoalveolar lavage at baseline (0 hr) and 2, 4, 6, 8, or 24 hours postchallenge. Cardiorespiratory variables were continuously recorded throughout the study day, and plasma and bronchoalveolar lavage fluid markers of inflammation were measured.
  
  
  RESULTS
  IV endotoxin elicited a systemic inflammatory response with a time-dependent increase and peak in tumor necrosis factor-α, interleukin-6, and leukocyte counts (all p < 0.001). Furthermore, a delayed (6-8 hr) increase in bronchoalveolar lavage fluid interleukin-6 concentration (p < 0.001) and alveolar leukocyte count (p = 0.03) and a minor increase in bronchoalveolar lavage fluid tumor necrosis factor-α were observed (p = 0.06). Endobronchial endotoxin was followed by progressive alveolar neutrocytosis and increased bronchoalveolar lavage fluid tumor necrosis factor-α, interleukin-6, and albumin (all p < 0.001); a systemic inflammatory response was observed after 2-4 hours, with no change in plasma tumor necrosis factor-α.
  
  
  CONCLUSIONS
  Acute lung or systemic inflammation in humans is followed by a transcompartmental proinflammatory response, the degree and differential kinetics of which suggests that the propagation of inflammation may depend on the primary site of injury.
authors.affiliation: 1Department of Intensive Care, University Hospital Rigshospitalet, Copenhagen Ø, Denmark. 2Centre of Inflammation and Metabolism, Department of Infectious Diseases M7641, University Hospital Rigshospitalet, Copenhagen Ø, Denmark. 3Neurovascular Research Laboratory, Faculty of Health, Science and Sport, University of Glamorgan, South Wales, United Kingdom. 4Centre for Clinical Education, University of Copenhagen and the Capital Region of Denmark, Copenhagen, Denmark. 5The Heart Centre, Department of Lung Transplantation, University Hospital Rigshospitalet, Copenhagen Ø, Denmark. 6Laboratory of Molecular Medicine, Department of Clinical Immunology M7631, University Hospital Rigshospitalet, Copenhagen Ø, Denmark. 7Neurointensive Care Unit 2093, Department of Neuroanesthesiology, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.
authors.forename: Ronni R
authors.initials: RR
authors.lastname: Plovsing
authors.forename: Ronan M G
authors.initials: RM
authors.lastname: Berg
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Evans
authors.forename: Lars
authors.initials: L
authors.lastname: Konge
authors.forename: Martin
authors.initials: M
authors.lastname: Iversen
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology; D061605:Administration, Intravenous; D000328:Adult; D015415:Biomarkers; D018893:Bronchoalveolar Lavage; D004311:Double-Blind Method; D004333:Drug Administration Routes; D004731:Endotoxins / Q000276:immunology*; D006439:Hemodynamics; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology*; D008297:Male; D011014:Pneumonia / Q000276:immunology; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004731:Endotoxins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli