A Muscarinic Antagonist Reduces Airway Inflammation and Bronchoconstriction Induced by Ambient Particulate Matter in a Mouse Model of Asthma

Jun Kurai, Masanari Watanabe, Hiroyuki Sano, Kyoko Iwata, Degejirihu Hantan and Eiji Shimizu
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Jun Kurai: Department of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan
Masanari Watanabe: Department of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan
Hiroyuki Sano: Department of Respiratory Medicine and Allergology, Kinki University, 377-2 Ohnohigashi, Osakasayama, Osaka 589-0014, Japan
Kyoko Iwata: Department of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan
Degejirihu Hantan: Department of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan
Eiji Shimizu: Department of Respiratory Medicine and Rheumatology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan

IJERPH, 2018, vol. 15, issue 6, 1-15

Abstract: Ambient particulate matter (PM) can increase airway inflammation and induce bronchoconstriction in asthma. This study aimed to investigate the effect of tiotropium bromide, a long-acting muscarinic antagonist, on airway inflammation and bronchoconstriction induced by ambient PM in a mouse model of asthma. We compared the effect of tiotropium bromide to that of fluticasone propionate and formoterol fumarate. BALB/c mice were sensitized to ovalbumin (OVA) via the airways and then administered tiotropium bromide, fluticasone propionate, or formoterol fumarate. Mice were also sensitized to ambient PM via intranasal instillation. Differential leukocyte counts and the concentrations of interferon (IFN)-γ, interleukin (IL)-5, IL-6, IL-13, and keratinocyte-derived chemokine (KC/CXCL1) were measured in bronchoalveolar lavage fluid (BALF). Diacron-reactive oxygen metabolites (dROMs) were measured in the serum. Airway resistance and airway inflammation were evaluated in lung tissue 24 h after the OVA challenge. Ambient PM markedly increased neutrophilic airway inflammation in mice with OVA-induced asthma. Tiotropium bromide improved bronchoconstriction, and reduced neutrophil numbers, decreased the concentrations of IL-5, IL-6, IL-13, and KC/CXCL1 in BALF. However, tiotropium bromide did not decrease the levels of dROMs increased by ambient PM. Though eosinophilic airway inflammation was reduced with fluticasone propionate, neutrophilic airway inflammation was unaffected. Bronchoconstriction was improved with formoterol fumarate, but not with fluticasone propionate. In conclusion, tiotropium bromide reduced bronchoconstriction, subsequently leading to reduced neutrophilic airway inflammation induced by ambient PM.

Keywords: airway inflammation; asthma; muscarinic antagonists; ovalbumin mouse model; particulate matter (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2018
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