Publications : 2012

Lamb DJ, Parker N, Ulrich K, Walsh R, Yeadon M, Evans SM. 2012. Characterisation of a mouse model of cigarette smoke extract-induced lung inflammation. J Pulmon Resp Med 2(3):open access, doi: 10.4172/2161-105X.1000125.


Aim: The aim of this study was to develop a lung-targeted, mouse model of cigarette smoke-induced inflammation that can be used to study the pathophysiological changes that occur in the lungs of human smokers and patients with chronic obstructive pulmonary disease (COPD).

Materials & Methods: Cigarette smoke extract (CSE) was prepared freshly daily. Intranasal administration into female mice was performed once daily for up to 3 weeks.

Results: CSE significantly increased airway macrophages after 3 and 4 days of dosing, and then declined over the subsequent 2 weeks. However, airway neutrophils were elevated after a single dose of CSE, and at all subsequent time points. Muc5AC was significantly increased in the Bronchoalveolar lavage (BAL) of CSE-treated animals compared to control mice (P<0.05), but TNF-α concentrations decreased in a dose-dependent manner. In animals challenged with CSE for 4 consecutive days, a PDE4 inhibitor (Roflumilast; 10 mg/kg BID) significantly inhibited both macrophages (P<0.01) and neutrophils (P<0.001), a steroid (prednisolone; 10 mg/kg BID) had no effect on either macrophages or neutrophils and an oral p38 inhibitor (PHA-818637; 10 mg/kg BID) inhibited macrophages (P<0.05), but not neutrophils. CSE inhibited lipopolysaccharide-induced airway neutrophilia.

Conclusion: This model reflects many aspects of human COPD including pulmonary leucocytes, mucin, TNF-α and response to clinical therapeutic agents and may be useful in assessing the efficacy of potential therapies.