title: Chlamydophila pneumoniae induces a sustained airway hyperresponsiveness and inflammation in mice.
abstract: BACKGROUND
  It has been reported that Chlamydophila (C.) pneumoniae is involved in the initiation and promotion of asthma and chronic obstructive pulmonary diseases (COPD). Surprisingly, the effect of C. pneumoniae on airway function has never been investigated.
  
  
  METHODS
  In this study, mice were inoculated intranasally with C. pneumoniae (strain AR39) on day 0 and experiments were performed on day 2, 7, 14 and 21.
  
  
  RESULTS
  We found that from day 7, C. pneumoniae infection causes both a sustained airway hyperresponsiveness and an inflammation. Interferon-gamma (IFN-gamma) and macrophage inflammatory chemokine-2 (MIP-2) levels in bronchoalveolar lavage (BAL)-fluid were increased on all experimental days with exception of day 7 where MIP-2 concentrations dropped to control levels. In contrast, tumor necrosis factor-alpha (TNF-alpha) levels were only increased on day 7. From day 7 to 21 epithelial damage and secretory cell hypertrophy was observed. It is suggested that, the inflammatory cells/mediators, the epithelial damage and secretory cell hypertrophy contribute to initiation of airway hyperresponsiveness.
  
  
  CONCLUSIONS
  Our study demonstrates for the first time that C. pneumoniae infection can modify bronchial responsiveness. This has clinical implications, since additional changes in airway responsiveness and inflammation-status induced by this bacterium may worsen and/or provoke breathlessness in asthma and COPD.
authors.affiliation: Institute of Respiratory Diseases, University of Milan, IRCCS Ospedale Maggiore Fondazione Policlinico-Mangiagalli-Regina Elena, Milano, Italy. francesco.blasi@unimi.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.forename: Stefano
authors.initials: S
authors.lastname: Aliberti
authors.forename: Luigi
authors.initials: L
authors.lastname: Allegra
authors.forename: Gioia
authors.initials: G
authors.lastname: Piatti
authors.forename: Paolo
authors.initials: P
authors.lastname: Tarsia
authors.forename: Jacobus M
authors.initials: JM
authors.lastname: Ossewaarde
authors.forename: Vivienne
authors.initials: V
authors.lastname: Verweij
authors.forename: Frans P
authors.initials: FP
authors.lastname: Nijkamp
authors.forename: Gert
authors.initials: G
authors.lastname: Folkerts
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000382:microbiology; D054426:Chemokine CXCL2 / Q000378:metabolism; D023521:Chlamydophila Infections / Q000150:complications* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D016993:Chlamydophila pneumoniae; D002923:Cilia / Q000382:microbiology / Q000648:ultrastructure; D004195:Disease Models, Animal; D006984:Hypertrophy; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D018410:Pneumonia, Bacterial / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000382:microbiology / Q000648:ultrastructure; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma