Effect of tiotropium bromide on airway remodeling in a chronic asthma model.

Abstract

BACKGROUND:

Recent evidence suggests that acetylcholine acting through muscarinic receptors may play an inhibitory role in the mechanisms that drive the structural changes in the airways called airway remodeling. The novel anticholinergic drug tiotropium bromide, which selectively antagonizes muscarinic receptors, especially the M3 subtype, and is long acting, could be beneficial in attenuating airway remodeling in chronic asthma.

OBJECTIVE:

To investigate the effect of tiotropium bromide on parameters of airway remodeling, including smooth muscle hypertrophy and peribronchial thickening, in a mouse model of chronic asthma.

METHODS:

To develop the murine models of acute and chronic asthma, BALB/c mice were sensitized and challenged to ovalbumin for 1 and 3 months, respectively. The effect of tiotropium bromide (0.1mM in 50 μL of phosphate-buffered saline) on pulmonary inflammation and remodeling was evaluated. The expression of muscarinic receptors M2 and M3 was analyzed.

RESULTS:

In the chronic asthma model, the tiotropium-treated group significantly decreased smooth muscle thickening and peribronchial collagen deposition. As for pulmonary inflammation, the chronic asthma model had a reduction of inflammatory cells and T(H)2 cytokines by tiotropium bromide, but the effects in the asthma acute model were reversed. In the chronic asthma model, expression of the M3 receptor was inhibited and that of the M2 receptor was elevated by the administration of tiotropium bromide.

CONCLUSION:

This study suggests that tiotropium bromide might have an inhibitory effect on airway remodeling in a murine model of chronic asthma. Differential effects on muscarinic receptor subtypes may explain why tiotropium bromide has different effects on acute and chronic asthma.

• Authors: Ji Young Kang, Chin Kook Rhee, Ju Sang Kim, Chan Kwon Park, Seung Joon Kim, Sang Haak Lee, Hyung Kyu Yoon, Soon Seog Kwon, Young Kyoon Kim, Sook Young Lee
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 109 Issue 1 Pg. 29-35 (Jul 2012) ISSN: 1534-4436 [Electronic] United States
• PMID: 22727154 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cholinergic Antagonists
• Cytokines
• Receptor, Muscarinic M2
• Receptor, Muscarinic M3
• Scopolamine Derivatives
• Ovalbumin
• Acetylcholine
• Tiotropium Bromide

Topics

• Acetylcholine (metabolism)
• Acute Disease
• Airway Remodeling (drug effects)
• Animals
• Asthma (drug therapy, immunology, pathology)
• Bronchoalveolar Lavage Fluid (cytology, immunology)
• Cholinergic Antagonists (therapeutic use)
• Chronic Disease
• Cytokines (drug effects)
• Disease Models, Animal
• Eosinophils (drug effects, immunology)
• Female
• Macrophages (drug effects, immunology)
• Mice
• Mice, Inbred BALB C
• Muscle, Smooth (drug effects)
• Neutrophils (drug effects, immunology)
• Ovalbumin (immunology)
• Pneumonia (drug therapy, metabolism)
• Receptor, Muscarinic M2 (antagonists & inhibitors)
• Receptor, Muscarinic M3 (antagonists & inhibitors)
• Scopolamine Derivatives (pharmacology, therapeutic use)
• Th2 Cells (drug effects, immunology)
• Tiotropium Bromide