Abstract
Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. The cysteinyl leukotrienes (LTC(4), D(4) and E(4)) are known to play important roles in the pathobiology of asthma. To evaluate the effect of low dose montelukast (MK) on the development of airway remodeling using a chronic murine model of allergic airway inflammation with subepithelial fibrosis, BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on days 0 and 14, received intranasal OVA periodically on days 14-75. MK treated mice received montelukast sodium intraperitoneally on days 26-75. The OVA sensitized/challenged mice developed an extensive eosinophil cell inflammatory response, goblet cell hyperplasia, mucus occlusion, and smooth muscle hypertrophy of the airways. In addition, in OVA sensitized/challenged mice, dense collagen deposition/fibrosis was seen throughout the lung interstitium surrounding the airways, blood vessels, and alveolar septae. The cysteinyl leukotriene 1 (CysLT1) receptor antagonist, MK significantly reduced the airway eosinophil infiltration, goblet cell hyperplasia, mucus occlusion, and lung fibrosis except airway smooth muscle hypertrophy in the OVA sensitized/challenged mice. The OVA sensitized/challenged mice had significantly increased epithelial desquamation compared with control mice. MK markedly reduced epithelial desquamation of airways in OVA/MK treated animals compared with OVA sensitized/challenged mice. MK treatment did not affect the levels of CysLT in lung tissue. Our results show that the important role of cysteinyl leukotrienes in the pathogenesis of asthma. Lower dose of CysLT1 receptor antagonism has a significant anti-inflammatory effect on allergen-induced lung inflammation and fibrosis but not airway smooth muscle hypertrophy in an animal model of asthma.
Highlights
The inflammatory process that characterizes the pathophysiology of asthma involves a number of cells and mediators
There was no significant difference in the levels of cysteinyl leukotrienes (CysLTs) between OVA sensitized/challenged mice and OVA/MK treatment animals (P = 0.293) (Figure 8). It was evaluated the effects of low dose leukotriene receptor antagonist, montelukast, on the airway remodeling for chronic asthma in a mouse model
Our findings suggest that pretreatment with low dose montelukast for chronic allergic asthma markedly decreased eosinophil infiltration into the lung interstitium, goblet cell hyperplasia with airway occlusion with mucus and increased collagen deposition around the airways and blood vessels without a significant decrease airway smooth muscle thickness
Summary
The inflammatory process that characterizes the pathophysiology of asthma involves a number of cells and mediators. Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling and include airway wall thickening, subepithelial fibrosis, and hyperplasia of mucus glands, myofibroblasts, smooth muscle, and vasculature (Elias et al, 1999). The cysteinyl leukotrienes (CysLTs; LTC4, D4, E4) are known to play an important role in the pathobiology of asthma. These compounds, derived from arachidonic acid via the 5-lipoxygenase pathway, are produced in cells of inflammation such as eosinophils, mast cells, monocytes, and basophiles (Lewis et al, 1990). The leukotrienes have multiple effects that contribute to the airways obstruction and inflammation that characterize asthma. It is widely recognized that CysLTs play an important role in asthma, participating in both the bronchoconstriction and the chronic inflammatory component of the disease
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