Chronic exposure to beta-blockers attenuates inflammation and mucin content in a murine asthma model.
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.
Nguyen
Long P
LP
Department of Pharmacological and Pharmaceutical Sciences, University of Houston, College of Pharmacy, 4800 Calhoun, Houston, TX 77204-5037, USA.
Omoluabi
Ozozoma
O
Parra
Sergio
S
Frieske
Joanna M
JM
Clement
Cecilia
C
Ammar-Aouchiche
Zoulikha
Z
Ho
Samuel B
SB
Ehre
Camille
C
Kesimer
Mehmet
M
Knoll
Brian J
BJ
Tuvim
Michael J
MJ
Dickey
Burton F
BF
Bond
Richard A
RA
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000188:drug therapy*; D007260:Infusion Pumps; D007274:Injections, Intraperitoneal; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009077:Mucins / Q000378:metabolism*; D009248:Nadolol / Q000008:administration & dosage / Q000494:pharmacology; D010047:Ovalbumin; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms
D000319:Adrenergic beta-Antagonists; D008024:Ligands; D009077:Mucins; D011412:Propanolamines; D009248:Nadolol; C026777:ICI 118551; D010047:Ovalbumin