title: LPS exacerbates functional and inflammatory responses to ovalbumin and decreases sensitivity to inhaled fluticasone propionate in a guinea pig model of asthma.
abstract: OBJECTIVE
  Asthma exacerbations contribute to corticosteroid insensitivity. LPS is ubiquitous in the environment. It causes bronchoconstriction and airway inflammation and may therefore exacerbate allergen responses. This study examined whether LPS and ovalbumin co-administration could exacerbate the airway inflammatory and functional responses to ovalbumin in conscious guinea pigs and whether these exacerbated responses were insensitive to inhaled corticosteroid treatment with fluticasone propionate (FP).
  
  
  METHODS
  Guinea pigs were sensitized and challenged with ovalbumin and airway function recorded as specific airway conductance by whole body plethysmography. Airway inflammation was measured from lung histology and bronchoalveolar lavage. Airway hyper-reactivity (AHR) to inhaled histamine was examined 24 h after ovalbumin. LPS was inhaled alone or 24 or 48 h before ovalbumin and combined with ovalbumin. FP (0.05-1 mg·mL(-1) ) or vehicle was nebulized for 15 min twice daily for 6 days before ovalbumin or LPS exposure.
  
  
  RESULTS
  Ovalbumin inhalation caused early (EAR) and late asthmatic response (LAR), airway hyper-reactivity to histamine and influx of inflammatory cells into the lungs. LPS 48 h before and co-administered with ovalbumin exacerbated the response with increased length of the EAR, prolonged response to histamine and elevated inflammatory cells. FP 0.5 and 1 mg·mL(-1) reduced the LAR, AHR and cell influx with ovalbumin alone, but was ineffective when guinea pigs were exposed to LPS before and with ovalbumin.
  
  
  CONCLUSIONS
  LPS exposure exacerbates airway inflammatory and functional responses to allergen inhalation and decreases corticosteroid sensitivity. Its widespread presence in the environment could contribute to asthma exacerbations and corticosteroid insensitivity in humans.
authors.affiliation: Cardiff School of Pharmacy, Cardiff University, Cardiff, UK.
authors.forename: A P P
authors.initials: AP
authors.lastname: Lowe
authors.forename: R S
authors.initials: RS
authors.lastname: Thomas
authors.forename: A T
authors.initials: AT
authors.lastname: Nials
authors.forename: E J
authors.initials: EJ
authors.lastname: Kidd
authors.forename: K J
authors.initials: KJ
authors.lastname: Broadley
authors.forename: W R
authors.initials: WR
authors.lastname: Ford
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004351:Drug Resistance / Q000187:drug effects; D000068298:Fluticasone / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D006632:Histamine / Q000009:adverse effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000276:immunology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D010047:Ovalbumin / Q000276:immunology*; D010993:Plethysmography, Whole Body
chemical_list: D008070:Lipopolysaccharides; D006632:Histamine; D010047:Ovalbumin; D000068298:Fluticasone