title: Lung function and inflammation during murine Pseudomonas aeruginosa airway infection.
abstract: BACKGROUND
  Following any acute irritation lung function declines rapidly. Reasons for pulmonary deterioration in humans had been attributed to the action of either interleukin-6 or interleukin-8 in the lungs.
  
  
  OBJECTIVE
  The present study investigates the association between immune response and decline in lung function in a murine bacterial lung infection model.
  
  
  METHODS
  Upon intratracheal inoculation of C57BL/6J mice with a sublethal dose of Pseudomonas aeruginosa lung function, cytokine, chemokine and cytometry in bronchoalveolar lavage fluid, bacterial counts and lung histology was assessed at 2, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96 and 120 h post inoculation.
  
  
  RESULTS
  Lung function measured by non-invasive head-out spirometry decreased most strongly between 6 and 10 h post inoculation and required up to 72 h to recover for selected parameters. CFU counts in the lungs peaked at 4h post inoculation with subsequent decline until at 24-48 h post inoculation background levels were reached. Cytokine and chemokine responses could be separated into an early pro-inflammatory phase (2-8h post inoculation; mainly tumor-necrosis factor α (TNFα) and interleukin-1α driven) and a late anti-inflammatory resolution phase (starting at 24h post inoculation; mainly interleukin-10 and interleukin-4 driven). Interleukin-6 levels correlated with the deterioration of lung function. Lung histology showed maximal changes in terms of inflammation and edema between 24 and 48 h post inoculation.
  
  
  CONCLUSIONS
  In summary, elevated interleukin-6, high local neutrophil counts and lung edema were found to be the most characteristic signs of the transient period of deterioration of lung function.
authors.affiliation: Pediatric Pulmonology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. woelbeling.florian@mh-hannover.de
authors.forename: Florian
authors.initials: F
authors.lastname: Wölbeling
authors.forename: Antje
authors.initials: A
authors.lastname: Munder
authors.forename: Tanja
authors.initials: T
authors.lastname: Kerber-Momot
authors.forename: Detlef
authors.initials: D
authors.lastname: Neumann
authors.forename: Christian
authors.initials: C
authors.lastname: Hennig
authors.forename: Gesine
authors.initials: G
authors.lastname: Hansen
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tümmler
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000276:immunology / Q000382:microbiology; D002404:Catheterization / Q000379:methods; D004487:Edema; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D016753:Interleukin-10 / Q000032:analysis / Q000096:biosynthesis; D053582:Interleukin-1alpha / Q000032:analysis / Q000096:biosynthesis; D015847:Interleukin-4 / Q000032:analysis / Q000096:biosynthesis; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000254:growth & development; D012129:Respiratory Function Tests; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
chemical_list: D053582:Interleukin-1alpha; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4