Anti-inflammatory agents and allergen-induced beta2-receptor dysfunction in isolated human bronchi

Am J Respir Crit Care Med. 1998 Dec;158(6):1809-14. doi: 10.1164/ajrccm.158.6.9801105.

Abstract

Antigen challenge causes beta2-adrenoceptor dysfunction in sensitized human bronchi (Am. J. Respir. Crit. 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 sensitized to house dust mite and challenged (1) with allergen only, (2) with allergen plus indomethacin (10(-)5 M), (3) with allergen plus nedocromil sodium (10(-)7 M to 10(-)5 M), (4) with allergen plus the H1-receptor antagonist cetirizine (10(-)7 M to 10(-)5 M), and (5) with allergen plus the peptido-leukotriene receptor antagonist iralukast (10(-)7 M to 10(-)5 M). Rings were first contracted with 10(-)6 M carbachol and then relaxed with salbutamol (10(-)9 M to 10(-)4 M). The concentration-relaxation curve to salbutamol was shifted significantly to the right in the rings challenged with allergen only compared with control rings. In the rings challenged with allergen plus nedocromil sodium (10(-)6 M and 10(-)5 M) or iralukast (10(-)6 M and 10(-)5 M) the concentration-relaxation curves to salbutamol were significantly shifted to the left compared with rings challenged in saline alone, suggesting a protective effect against beta2-adrenoceptor dysfunction. Neither allergen plus cetirizine nor allergen plus indomethacin shifted significantly the concentration-relaxation curves to salbutamol compared with rings challenged in saline alone. We conclude that the release of peptido-leukotrienes may play a significant role in causing the allergen-induced beta2-receptor dysfunction in passively sensitized human bronchi.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Albuterol / administration & dosage
  • Albuterol / pharmacology
  • Allergens / immunology
  • Allergens / pharmacology*
  • Animals
  • Anti-Allergic Agents / administration & dosage
  • Anti-Allergic Agents / pharmacology
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Benzopyrans / pharmacology*
  • Bronchi / drug effects*
  • Bronchi / immunology
  • Bronchoconstrictor Agents / administration & dosage
  • Bronchoconstrictor Agents / pharmacology
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / pharmacology
  • Carbachol / administration & dosage
  • Carbachol / pharmacology
  • Cetirizine / administration & dosage
  • Cetirizine / pharmacology
  • Cholinergic Agonists / administration & dosage
  • Cholinergic Agonists / pharmacology
  • Culture Techniques
  • Dose-Response Relationship, Drug
  • Female
  • Histamine H1 Antagonists / administration & dosage
  • Histamine H1 Antagonists / pharmacology
  • Humans
  • Immunization
  • Indomethacin / administration & dosage
  • Indomethacin / pharmacology
  • Leukotriene Antagonists / administration & dosage
  • Leukotriene Antagonists / pharmacology
  • Male
  • Middle Aged
  • Mites / immunology
  • Nedocromil / administration & dosage
  • Nedocromil / pharmacology
  • Receptors, Adrenergic, beta / drug effects*
  • Receptors, Adrenergic, beta / immunology

Substances

  • Allergens
  • Anti-Allergic Agents
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzopyrans
  • Bronchoconstrictor Agents
  • Bronchodilator Agents
  • Cholinergic Agonists
  • Histamine H1 Antagonists
  • Leukotriene Antagonists
  • Receptors, Adrenergic, beta
  • Nedocromil
  • Carbachol
  • iralukast
  • Albuterol
  • Indomethacin
  • Cetirizine