[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.

Material and 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.