Published ahead of print on December 20, 2007, doi:10.1165/rcmb.2007-0279RC Am. J. Respir. Cell Mol. Biol., Volume 38, Number 3, March 2008, 256-262 A more recent version of this article appeared on March 1, 2008
Submitted on July 23, 2007 Chronic Exposure to Beta-Blockers Attenuates Inflammation and Mucin Content in a Murine Asthma ModelLong P Nguyen1,1 Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX, USA, 2 Department of Biology and Biochemistry, University of Houston, Houston, TX, USA, 3 Department of Pulmonary Medicine, M.D. Anderson Cancer Center, Houston, TX, USA; Texas A and M University System Houston Health Science Center, Institute of Biosciences and Technology, Houston, TX, USA, 4 Department of Medicine, Veterans Affairs San Diego Healthcare System and University of California, San Diego, CA, USA, 5 Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, NC, USA * To whom correspondence should be addressed. E-mail: RABond{at}uh.edu.
Single dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits 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-
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1 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 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 where beta-blockers producing an acutely detrimental effect may provide a therapeutically beneficial effect with chronic administration.
