title: Aspiration pneumonitis primes the host for an exaggerated inflammatory response during pneumonia.
abstract: OBJECTIVE
  Nosocomial pneumonia is a feared complication in the critically ill patient. Aspiration pneumonitis is frequently complicated by infections. The objective of this study was to determine the influence of aspiration pneumonitis on the host response to a common nosocomial respiratory pathogen.
  
  
  METHODS
  Controlled, in vivo laboratory study.
  
  
  METHODS
  Research laboratory of a health sciences university.
  
  
  METHODS
  Female C57Bl/6 mice.
  
  
  METHODS
  Mice received hydrochloric acid or saline intratracheally followed 16 hrs later by Klebsiella pneumoniae.
  
  
  RESULTS
  Hydrochloric acid induced a mild aspiration pneumonitis. Nonetheless, hydrochloric acid aspiration resulted in a markedly increased inflammatory response in the lung on infection with K. pneumoniae. This enhanced inflammatory reaction was accompanied by a greatly increased outgrowth of K. pneumoniae in lungs of mice previously exposed to hydrochloric acid. Preexisting aspiration pneumonitis also triggered mouse lungs in vivo and alveolar macrophages ex vivo for enhanced release of proinflammatory mediators on stimulation with Klebsiella lipopolysaccharide. Inhibition of tumor necrosis factor-alpha resulted in an increased inflammatory reaction and enhanced bacterial outgrowth in mice with primary K. pneumoniae pneumonia, whereas it had no effect in mice with preexisting aspiration pneumonitis.
  
  
  CONCLUSIONS
  These data indicate a) that aspiration pneumonitis renders the host more susceptible to respiratory tract infection with K. pneumoniae, concurrently priming the lung for an exaggerated inflammatory response; and b) that although tumor necrosis factor-alpha plays a major role in the host response to primary infection, it does not affect lung inflammation or defense after aspiration pneumonitis.
authors.affiliation: Divisions of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: David J
authors.initials: DJ
authors.lastname: van Westerloo
authors.forename: Sylvia
authors.initials: S
authors.lastname: Knapp
authors.forename: Cornelis
authors.initials: C
authors.lastname: van't Veer
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003428:Cross Infection / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000503:physiopathology*; D007711:Klebsiella pneumoniae; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011015:Pneumonia, Aspiration / Q000276:immunology* / Q000382:microbiology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha