Anti-inflammatory agents and allergen-induced beta(2)-receptor dysfunctionin isolated human bronchi

Antigen challenge causes beta(2)-adrenoceptor dysfunction in sensitized hum an bronchi (Am. J. Respir. Grit. Care Med. 1997;155:1230-1234). This study investigated whether the dysfunction can be prevented by anti-inflammatory agents. Human bronchial rings (2 to 4 mm) from surgery were passively sensi tized to house dust mite and challenged (1) with allergen only, (2) with al lergen plus indomethacin (10(-5) M), (3) with allergen plus nedocromil sodi um (10(-7) M to 10(-5) M), (4) with allergen plus the H-1-receptor antagoni st cetirizine (10(-7) M to 10(-5) M), and (5) with allergen plus the peptid o-leukotriene receptor antagonist iralukast (10(-7) M to 10(-5) M). Rings w ere first contracted with 10(-6) M carbachol and then relaxed with salbutam ol (10(-9) M to 10(-4) M). The concentration-relaxation curve to salbutamol was shifted significantly to the right in the rings challenged with allerg en only compared with control rings. In the rings challenged with allergen plus nedocromil sodium (10(-6) M and 10(-5) NI) or iralukast (10(-6) M and 10(-5) M) the concentration-relaxation curves to salbutamol were significan tly shifted to the left compared with rings challenged in saline alone, sug gesting a protective effect against beta(2)-adrenoceptor dysfunction. Neith er allergen plus cetirizine nor allergen plus indomethacin shifted signific antly the concentration-relaxation curves to salbutamol compared with rings challenged in saline alone. We conclude that the release of peptido-leukot rienes may play a significant role in causing the allergen-induced beta(2)- receptor dysfunction in passively sensitized human bronchi.