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 (OVA) challenge, assessing mast cell activity and airway response in a murine model of asthma. Material and methods Mice were sensitized to OVA (10 μg injected intraperitoneally) and further challenged with 0.5% intranasal OVA. 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 OVA. The severity of airway inflammation was evaluated by means of a scoring system. Finally, the serum level of mouse mast cell protease (mMCP)-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 100 mg/mL. A clear trend toward worsening airway inflammation in the presence of rofecoxib was observed, although the difference between rofecoxibtreated 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 OVA-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.