The effects of low dose leukotriene receptor antagonist therapy on airway remodeling and cysteinyl leukotriene expression in a mouse asthma model

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.

Arachidonic Acid Metabolism as a Potential Mediator of Cardiac Fibrosis Associated with Inflammation

“…The fibrogenic potential of various types of silica is related to the degree of both cytotoxicity and stimulation of 5-LO products (9). A recent study has shown that a specific leukotriene receptor antagonist reduces pulmonary fibrosis in an animal model of asthma (10), although, surprisingly, no studies with this drug class have yet been published for cardiac fibrosis. As we shall show herein, there is now ample circumstantial evidence linking eicosanoids with the development of cardiac fibrosis.…”

Montelukast treatment (cysteinyl leukotriene receptor antagonist) in a model of food allergy: modifications in lymphatic cell population from rectal mucosa

“…Different authors describe inhibition of the eosinophils infiltration after the use of montelukast in different animal and human models, mainly in the respiratory system (3,4). The absence of statistically significant differences in the quantity of eosinophils observed among the groups studied is probably due to different characteristics of rectal mucosa model as compared to bronchial mucosa (32,33).…”

“…Montelukast is a cysteinyl-leukotriene receptor antagonist (CysLT) which actively and selectively blocks the leukotriene D4 (LTD4) receptor, which has shown an inhibition of allergy response in different animal and human models (1)(2)(3)(4)(5)(6).…”

Comparison of the efficacy of prednisolone, montelukast, and omalizumab in an experimental allergic rhinitis model

“…In experimental asthma models, montelukast was shown to decrease lung inflammation by inhibiting eosinophil trafficking/ degranulation, Th2 cytokine release, and structural changes in the lungs (13)(14)(15)17,21 (17) showed that montelukast treatment decreased contraction in small bronchi after challenge with LTD4 and OVA. Montelukast also inhibited plasma protein extravasation and eosinophilic infiltration in the airway epithelium, airway walls, and alveolar connections.…”

“…Previously, montelukast has been shown to decrease nasal symptoms and the number of eosinophils in nasal mucosa and lung tissue, inhibit the production and release of inflammatory cytokines, and reverse structural changes in the lungs (13)(14)(15)(16)(17). However, there are no studies showing the efficacy of omalizumab in an experimental allergy model.…”