title: Aclidinium bromide abrogates allergen-induced hyperresponsiveness and reduces eosinophilia in murine model of airway inflammation.
abstract: Airway hyperresponsiveness and inflammation characterize the airways of individuals with asthma and chronic obstructive pulmonary disease (COPD). Hence, therapeutic approaches that attenuate such manifestations may offer promise in the management of these diseases. In the present study, we investigated whether a novel long-acting cholinergic antagonist, aclidinium bromide, modulates airway function and leukocyte trafficking in an Aspergillus fumigatus (Af)-induced murine model of asthma. Nebulized aclidinium (1 mg/ml) administration completely abrogated increases in methacholine-induced lung resistance in Af-exposed mice. Parallel assessment of dynamic compliance showed that aclidinium also completely restores methacholine-mediated decreases in naïve and Af-exposed mice. As evidenced by differential cell counts within bronchoalveolar lavage fluid, aclidinium also diminished (51±4%) Af-induced airway eosinophil numbers with no significant change in other immune cell types. Further assessment of cytokine and total protein levels in bronchoalveolar lavage fluid showed that aclidinium had little effect on IL-4 or IL-6 levels in either Af-exposed or naïve mice but markedly decreased total protein levels in bronchoalveolar lavage fluid. These data suggest that aclidinium, a selective muscarinic antagonist, not only acts as a bronchodilator but could also act as an anti-inflammatory agent with potential clinical benefits in the treatment of COPD and asthma.
authors.affiliation: Airways Biology Initiative, Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Gautam
authors.initials: G
authors.lastname: Damera
authors.forename: Meiqi
authors.initials: M
authors.lastname: Jiang
authors.forename: Hengjiang
authors.initials: H
authors.lastname: Zhao
authors.forename: Homer W
authors.initials: HW
authors.lastname: Fogle
authors.forename: William F
authors.initials: WF
authors.lastname: Jester
authors.forename: Jose
authors.initials: J
authors.lastname: Freire
authors.forename: Reynold A
authors.initials: RA
authors.lastname: Panettieri
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000946:Antigens, Fungal / Q000276:immunology; D001249:Asthma / Q000188:drug therapy; D001991:Bronchitis / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D016207:Cytokines / Q000032:analysis; D005260:Female; D007249:Inflammation / Q000517:prevention & control*; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D011657:Pulmonary Eosinophilia / Q000517:prevention & control*; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D012137:Respiratory System / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D014326:Tropanes / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000946:Antigens, Fungal; D018680:Cholinergic Antagonists; D016207:Cytokines; D014326:Tropanes; C542859:aclidinium bromide