title: [A cyclooxygenase-2 selective inhibitor worsens respiratory function and enhances mast cell activity in ovalbumin-sensitized mice].
abstract: BACKGROUND
  Cyclooxygenase (COX)-2 activity has been said to have a protective effect in asthmatic patients as a result of prostaglandin E(2) production. In order to elucidate the mechanisms involved, we evaluated the impact of selective inhibition of COX-2 with rofecoxib during ovalbumin challenge, assessing mast cell activity and airway response in a murine model of asthma.
  
  
  METHODS
  Mice were sensitized to ovalbumin (10 microg injected intraperitoneally) and further challenged with 0.5% intranasal ovalbumin. Half the sensitized animals were treated orally with rofecoxib (15 mg/kg/d during the challenge phase). Lung function was measured by whole body plethysmography before and after exposure to ovalbumin. The severity of airway inflammation was evaluated by means of a scoring system. Finally, the serum level of mouse mast cell protease-1 was determined as an indicator of mucosal mast cell activity.
  
  
  RESULTS
  Sensitized mice treated with rofecoxib exhibited 2.4-fold greater airway hyperresponsiveness than did vehicle-treated mice at a methacholine concentration of 100mg/ml. A clear trend toward worsening airway inflammation in the presence of rofecoxib was observed, although the difference between rofecoxib-treated and vehicle-treated animals was not significant. These changes were accompanied by a significant increase in mucosal mast cell activity.
  
  
  CONCLUSIONS
  Selective pharmacological inhibition of COX-2 during the challenge phase worsens airway function in the ovalbumin -induced murine model of acute asthma. We suggest that this effect might be at least partially explained by the increase in airway mast cell activity.
authors.affiliation: Departamento de Farmacología, Universitat Autònoma de Barcelona, Barcelona, España.
authors.forename: Rosa
authors.initials: R
authors.lastname: Torres
authors.forename: Mónica
authors.initials: M
authors.lastname: Pérez
authors.forename: Alberto
authors.initials: A
authors.lastname: Marco
authors.forename: César
authors.initials: C
authors.lastname: Picado
authors.forename: Fernando
authors.initials: F
authors.lastname: de Mora