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Montelukast reduces inhaled chlorine triggered airway hyperresponsiveness and airway inflammation in the mouse
- Source :
- British Journal of Pharmacology. 174:3346-3358
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Background and Purpose Cysteinyl leukotrienes (CysLTs) are pro-inflammatory lipid mediators that exacerbate disease state in several asthma phenotypes including asthma induced by allergen, virus and exercise. However, the role of CysLTs in irritant-induced airway disease is not well characterized. The purpose of the current study was to investigate the effect of montelukast, a CysLT1 receptor antagonist, on parameters of irritant-induced asthma induced by inhalation of chlorine in the mouse. Experimental Approach BALB/c mice were exposed to chlorine in air (100 ppm, for 5 min). Montelukast (3 mg·kg−1) or the vehicle (1% methylcellulose) was administered 24 and 1 h prior to chlorine exposure and 1 h prior to outcome measurements. Twenty-four hours after exposure, responses to inhaled aerosolized methacholine, cell composition and an array of cytokines/chemokines in bronchoalveolar lavage (BAL) fluid were measured. Neutralizing antibodies against IL-6 and VEGF were administered prior to exposures. Key Results Montelukast reduced chlorine -induced airway hyperresponsiveness (AHR) to methacholine in the peripheral lung compartment as estimated from dynamic elastance, but not in large conducting airways. Montelukast treatment attenuated chlorine-induced macrophage influx, neutrophilia and eosinophilia in BAL fluid. Chlorine exposure increased VEGF, IL-6, the chemokines KC and CCL3 in BAL fluid. Montelukast treatment prevented chlorine-induced increases in VEGF and IL-6. Anti-IL-6 antibody inhibited chlorine-induced neutrophilia and reduced AHR. Conclusions and Implications Pre-treatment with montelukast attenuated chlorine-induced neutrophilia and AHR in mice. These effects are mediated, in part, via IL-6.
- Subjects :
- 0301 basic medicine
03 medical and health sciences
0302 clinical medicine
polycyclic compounds
Medicine
Eosinophilia
Montelukast
Asthma
Pharmacology
Lung
medicine.diagnostic_test
Inhalation
business.industry
respiratory system
medicine.disease
Neutrophilia
respiratory tract diseases
3. Good health
030104 developmental biology
medicine.anatomical_structure
Bronchoalveolar lavage
030228 respiratory system
Immunology
Methacholine
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 00071188
- Volume :
- 174
- Database :
- OpenAIRE
- Journal :
- British Journal of Pharmacology
- Accession number :
- edsair.doi...........592e4f698ef88d9785ff9130ed317a85