Chronic Exposure to Beta-Blockers Attenuates Inflammation and Mucin Content in a Murine Asthma Model

• Published in: American journal of respiratory cell and molecular biology Vol. 38; no. 3; pp. 256 - 262
• Main Authors: Nguyen, Long P, Omoluabi, Ozozoma, Parra, Sergio, Frieske, Joanna M, Clement, Cecilia, Ammar-Aouchiche, Zoulikha, Ho, Samuel B, Ehre, Camille, Kesimer, Mehmet, Knoll, Brian J, Tuvim, Michael J, Dickey, Burton F, Bond, Richard A
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01.03.2008; American Thoracic Society
• Subjects: Administration, Oral; Adrenergic beta-Antagonists - administration & dosage; Adrenergic beta-Antagonists - pharmacology; Animals; Asthma - drug therapy; Asthma - physiopathology; Disease Models, Animal; Female; Inflammation - drug therapy; Infusion Pumps; Injections, Intraperitoneal; Ligands; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mucins - metabolism; Nadolol - administration & dosage; Nadolol - pharmacology; Ovalbumin; Propanolamines - administration & dosage; Propanolamines - pharmacology; Rapid Communications; Specific Pathogen-Free Organisms
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2007-0279RC

Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that occurred with the use of beta-blockers in congestive heart failure, we previously determined that chronic administration of beta-blockers decreased AHR in a murine model of asthma. To elucidate the mechanisms for the beneficial effects of beta-blockers, we examined the effects of chronic administration of several beta-adrenoceptor ligands in a murine model of allergic asthma. Administration of beta-blockers resulted in a reduction in total cell counts, eosinophils, and the cytokines IL-13, IL-10, IL-5, and TGF-beta1 in bronchoalveolar lavage, and attenuated epithelial mucin content and morphologic changes. The differences in mucin content also occurred if the beta-blockers were administered only during the ovalbumin challenge phase, but administration of beta-blockers for 7 days was not as effective as administration for 28 days. These results indicate that in a murine model of asthma, chronic administration of beta-blockers reduces inflammation and mucous metaplasia, cardinal features of asthma that may contribute to airflow obstruction and AHR. Similar to heart failure, our results provide a second disease model in which beta-blockers producing an acutely detrimental effect may provide a therapeutically beneficial effect with chronic administration.