title: Longitudinal characterization of a model of chronic allergic lung inflammation in mice using imaging, functional and immunological methods.
abstract: The present study investigated the role that imaging could have for assessing lung inflammation in a mouse model of HDM (house dust mite)-provoked allergic inflammation. Inflammation is usually assessed using terminal procedures such as BAL (bronchoalveolar lavage) and histopathology; however, MRI (magnetic resonance imaging) and CT (computed tomography) methods have the potential to allow longitudinal, repeated study of individual animals. Female BALB/c mice were administered daily either saline, or a solution of mixed HDM proteins sufficient to deliver a dose of 12 or 25 μg total HDM protein±budesonide (1 mg/kg of body weight, during weeks 5-7) for 7 weeks. AHR (airway hyper-responsiveness) and IgE measurements were taken on weeks 3, 5 and 7. Following imaging sessions at weeks 3, 5 and 7 lungs were prepared for histology. BAL samples were taken at week 7 and lungs prepared for histology. MRI showed a gradual weekly increase in LTI (lung tissue intensity) in animals treated with HDM compared with control. The 25 μg HDM group showed a continual significant increase in LTI between weeks 3 and 7, the 12 μg HDM-treated group showed a similar rate of increase, and plateaued by week 5. A corresponding increase in AHR, cell counts and IgE were observed. CT showed significant increases in lung tissue density from week 1 of HDM exposure and this was maintained throughout the 7 weeks. Budesonide treatment reversed the increase in tissue density. MRI and CT therefore provide non-invasive sensitive methods for longitudinally assessing lung inflammation. Lung tissue changes could be compared directly with the classical functional and inflammatory readouts, allowing more accurate assessments to be made within each animal and providing a clinically translatable approach.
authors.affiliation: Respiratory Therapeutic Area, GlaxoSmithKline, Stevenage, Hertfordshire, UK. kumar.k.changani@gsk.com
authors.forename: Kumar
authors.initials: K
authors.lastname: Changani
authors.forename: Catherine
authors.initials: C
authors.lastname: Pereira
authors.forename: Simon
authors.initials: S
authors.lastname: Young
authors.forename: Robert
authors.initials: R
authors.lastname: Shaw
authors.forename: Simon P
authors.initials: SP
authors.lastname: Campbell
authors.forename: Kashmira
authors.initials: K
authors.lastname: Pindoria
authors.forename: Steve
authors.initials: S
authors.lastname: Jordan
authors.forename: Katherine
authors.initials: K
authors.lastname: Wiley
authors.forename: Sarah
authors.initials: S
authors.lastname: Bolton
authors.forename: Tony
authors.initials: T
authors.lastname: Nials
authors.forename: Michael
authors.initials: M
authors.lastname: Haase
authors.forename: Mike
authors.initials: M
authors.lastname: Pedrick
authors.forename: Richard
authors.initials: R
authors.lastname: Knowles
mesh_terms: D000818:Animals; D015415:Biomarkers; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D008137:Longitudinal Studies; D008168:Lung / Q000000981:diagnostic imaging* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000000981:diagnostic imaging / Q000473:pathology; D039981:Pyroglyphidae / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000000981:diagnostic imaging* / Q000473:pathology; D015656:Respiratory Mechanics; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers