Chronic exposure to beta-blockers attenuates inflammation and mucin content in a murine asthma model

Long P. Nguyen, Ozozoma Omoluabi, Sergio Parra, Joanna M. Frieske, Cecilia Clement, Zoulikha Ammar-Aouchiche, Samuel B. Ho, Camille Ehre, Mehmet Kesimer, Brian J. Knoll, Michael J. Tuvim, Burton F. Dickey, Richard A. Bond

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

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-β1 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.

Original languageEnglish (US)
Pages (from-to)256-262
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2008

Keywords

  • Airway inflammation
  • Asthma
  • Beta-adrenoceptor
  • Beta-blockers
  • Mucin

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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