Bronchial hyperreactivity occurs in steroid-treated guinea pigs depleted of leukocytes by cyclophosphamide

The effects of cyclophosphamide and cortisone acetate treatment on O3-induced changes in airway mucosal morphology and bronchial reactivity were assessed in guinea pigs. Animals in groups of four were studied at 2 or 6 h after O3 (3.0 ppm, 2 h) and in one control group. Reactivity was determined by measuring specific airway resistance during intravenous acetylcholine infusion in intact, unanesthetized, spontaneously breathing animals. After testing, tracheal tissue was obtained from all animals for light microscopic examination. Another group of 10 drug-treated and 10 normal animals were tested at 2 h, 6 h, 1 day, and 4 days after O3. Drug treatment resulted in substantial decreases in both circulating and airway mucosal granulocytes. Two hours after O3, a marked decrease in airway mucosal goblet cells as well as ciliated cell damage occurred in both normal and treated animals. However, only in normal animals did neutrophilic infiltration develop thereafter. Nonetheless, hyperreactivity postozone occurred and progressed similarly in both groups. Our results indicate that acute O3-induced bronchial hyperreactivity at 2 h is associated with signs of airway mucosal injury but appears independent of granulocyte changes. Airway neutrophilic infiltration and eosinophil depletion seem to be consequences of mucosal injury from O3 and not causes of the bronchial hyperreactivity that results.