title: A murine model of cigarette smoke-induced pulmonary inflammation using intranasally administered smoke-conditioned medium.
abstract: To date, few animal models of chronic obstructive pulmonary disease (COPD) exist that are ideal for the evaluation of pathophysiology, as they typically require many months of cigarette smoke exposure in inhalation facilities. Here we show that pulmonary inflammation and some of the inflammatory hallmarks of COPD can be induced in mice by cigarette smoke-conditioned media (CS) administered by the intranasal route. Balb/c mice were challenged with CS for up to 40 days. At the end of smoke treatment, mice were sacrificed and bronchoalveolar lavage (BAL) fluid collected. Total cell counts and cell differentials were performed. Enzyme-linked immunosorbent assays (ELISAs) for KC and tumor necrosis factor alpha (TNF-alpha) were performed on BAL fluid. Lungs and nasal cavities were examined histologically. Intranasal CS treatment significantly increased BAL neutrophils, lymphocytes, KC, TNF-alpha, and mucin. Changes in pulmonary reactivity to methacholine were also observed in mice challenged with CS for 40 days. The model described above demonstrates that within 1 to 8 weeks of intranasal instillation of CS, mice develop pulmonary inflammation and cellular lung changes that are characteristic of human COPD and therefore may be a good short-term in vivo model that can be utilized to monitor intervention strategies targeted for COPD.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, USA. miller_laura@allergan.com
authors.forename: Laura M
authors.initials: LM
authors.lastname: Miller
authors.forename: W Michael
authors.initials: WM
authors.lastname: Foster
authors.forename: Donna M
authors.initials: DM
authors.lastname: Dambach
authors.forename: Darryl
authors.initials: D
authors.lastname: Doebler
authors.forename: Murray
authors.initials: M
authors.lastname: McKinnon
authors.forename: Loran
authors.initials: L
authors.lastname: Killar
authors.forename: Malinda
authors.initials: M
authors.lastname: Longphre
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*; D013045:Species Specificity; D014026:Nicotiana
chemical_list: D012906:Smoke