Aclidinium bromide abrogates allergen-induced hyperresponsiveness and reduces eosinophilia in murine model of airway inflammation

Airways Biology Initiative, Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
European journal of pharmacology (Impact Factor: 2.53). 12/2010; 649(1-3):349-53. DOI: 10.1016/j.ejphar.2010.09.043
Source: PubMed


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.

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    • "These data suggest that anticholinergics such as tiotropium bromide in COPD (Oenema et al., 2010; Wollin and Pieper, 2010) may offer value in IL-8-dependent airway inflammation. In addition to inhibiting AHR, other M3R antagonists such as aclidinium bromide have substantial pharmacological benefits by inhibiting airway eosinophilia in murine models of asthma (Damera et al., 2010). Whether mast cell-derived histamine stimulates IL-8 secretion in ASM remains unknown; however, b-tryptase, another mast cellderived serine protease, substantially enhances IL-8 via transcriptional and post-transcriptional mechanisms (Mullan et al., 2008). "
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