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

Am J Respir Cell Mol Biol. 2008 Mar;38(3):256-62. doi: 10.1165/rcmb.2007-0279RC. Epub 2007 Dec 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Specific Pathogen-Free Organisms


  • Adrenergic beta-Antagonists
  • Ligands
  • Mucins
  • Propanolamines
  • Nadolol
  • ICI 118551
  • Ovalbumin