Tiotropium reduction of lung inflammation in a model of chronic gastro-oesophageal reflux.
Gastro-oesophageal reflux is frequent in chronic airway diseases and is considered a trigger for symptoms. In animal models, bilateral vagotomy or muscarinic antagonists prevent the increase in airway resistance and the microvascular leakage induced by acute oesophageal acid instillation. The present study investigates lung inflammation and remodelling in an animal model of chronic gastro-oesophageal reflux disease (GORD), and the effectiveness of pretreatments with tiotropium, atropine and dexamethasone. Mice were exposed to twice-daily intra-oesophageal HCl instillations for 21 days. Exposure to HCl causes: marked infiltration by inflammatory cells of the airways and of peribronchial areas; an increase in epithelial thickness; histological features of interstitial pneumonitis; an increase in cell numbers and in the levels of interleukin-8; and soluble intercellular adhesion molecule in bronchoalveolar lavage fluids, as well as of in vitro tracheal contractility. The administration of nebulised tiotropium or intraperitoneal atropine prior to each instillation of HCl, considerably inhibited all these changes. These results indicate a major role of acetylcholine in airway inflammation and remodelling in a GORD model, and demonstrate that tiotropium and atropine can prevent lung inflammation with an effectiveness similar to intraperitoneal dexamethasone, providing additional evidence that anticholinergics might contribute to the control of inflammatory processes in airway diseases.
Cui
Y
Y
Dept of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Devillier
P
P
Kuang
X
X
Wang
H
H
Zhu
L
L
Xu
Z
Z
Xia
Z
Z
Zemoura
L
L
Advenier
C
C
Chen
H
H
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002908:Chronic Disease; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004941:Esophagitis / Q000139:chemically induced / Q000150:complications; D005764:Gastroesophageal Reflux / Q000139:chemically induced / Q000150:complications*; D006851:Hydrochloric Acid / Q000494:pharmacology; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D012602:Scopolamine Derivatives / Q000494:pharmacology*; D000069447:Tiotropium Bromide; D014132:Trachea / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D001285:Atropine; D003907:Dexamethasone; D000109:Acetylcholine; D006851:Hydrochloric Acid; D000069447:Tiotropium Bromide