INHIBITION OF PULMONARY EOSINOPHILIA DOES NOT NECESSARILY PREVENT THEAIRWAY HYPERRESPONSIVENESS INDUCED BY SEPHADEX BEADS

Background: The Lewis rat among highly inbred strains exhibits signifi cant airway hyperresponsiveness (AHR) following intravenous administra tion of Sephadex G-200 (Sephadex). The aim of this study was to invest igate the association of Sephadex-induced AHR with changes in airway i nflammation in Lewis rats. Methods: A suspension (0.5 mg/ml/rat) of Se phadex was intravenously administered to male Lewis rats on days 0, 2 and 5. Measurement of airway responsiveness to serotonin, bronchoalveo lar lavage (BAL) and histological study were performed on day 2-11. Re sults: Significant AHR induced by Sephadex was recognized on day 2 (p< 0.05), and AHR reached a maximum on day 7 (p<0.001). In the BAL study, eosinophils increased on day 2 (p<0.01) with a peak on day 5 (p<0.05) . In the histological study, we found Sephadex beads trapped in small arteries of the lung and granulomatous arteritis on day 2 or later. Pu lmonary granulomas, horseshoe-shaped multinuclear giant cells, eosinop hils and goblet cell hyperplasia were observed on day 2, and the degre e became intense on day 5-7. GCC-AP0341 (10 mg/kg, i.p. x3) inhibited the recruitment of eosinophils in BAL fluid and in lung tissue, but it did not inhibit AHR. The compound also inhibited pulmonary granulomas and goblet cell hyperplasia. Conclusion: The mechanism of Sephadex-in duced AHR may not be directly associated with inflammatory changes suc h as recruitment of eosinophils, pulmonary granulomas and hyperplasia of goblet cells in rats.