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Am J Respir Cell Mol Biol. 2008 Mar;38(3):256-62. Epub 2007 Dec 20.

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

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1
Department of Pharmacological and Pharmaceutical Sciences, University of Houston, College of Pharmacy, 4800 Calhoun, Houston, TX 77204-5037, USA.

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-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.

Comment in

PMID:
18096872
PMCID:
PMC2258446
DOI:
10.1165/rcmb.2007-0279RC
[Indexed for MEDLINE]
Free PMC Article
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