title: Airway hyper-responsiveness in lipopolysaccharide-challenged common marmosets (Callithrix jacchus).
abstract: Animal models with a high predictive value for human trials are needed to develop novel human-specific therapeutics for respiratory diseases. The aim of the present study was to examine lung-function parameters in marmoset monkeys (Callithrix jacchus) that can be used to detect pharmacologically or provocation-induced AHR (airway hyper-responsiveness). Therefore a custom-made lung-function device that allows application of defined aerosol doses during measurement was developed. It was hypothesized that LPS (lipopolysaccharide)-challenged marmosets show AHR compared with non-challenged healthy subjects. Invasive plethysmography was performed in 12 anaesthetized orotracheally intubated and spontaneously breathing marmosets. Pulmonary data of R(L) (lung resistance), C(dyn) (dynamic compliance), EF50 (mid-expiratory flow), P(oes) (oesophageal pressure), MV (minute volume), respiratory frequency (f) and V(T) (tidal volume) were collected. Measurements were conducted under baseline conditions and under MCh (methacholine)-induced bronchoconstriction. The measurement was repeated with the same group of animals after induction of an acute lung inflammation by intratracheal application of LPS. PDs (provocative doses) of MCh to achieve a certain increase in RL were significantly lower after LPS administration. AHR was demonstrated in the LPS treated compared with the naïve animals. The recorded lung-function data provide ground for pre-clinical efficacy and safety testing of anti-inflammatory substances in the common marmoset, a new translational NHP (non-human primate) model for LPS-induced lung inflammation.
authors.affiliation: ‡Pathology Unit, German Primate Center, Leibniz-Institute, Kellnerweg 4, 37077 Göttingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Curths
authors.forename: Judy
authors.initials: J
authors.lastname: Wichmann
authors.forename: Sarah
authors.initials: S
authors.lastname: Dunker
authors.forename: Horst
authors.initials: H
authors.lastname: Windt
authors.forename: Heinz-Gerd
authors.initials: HG
authors.lastname: Hoymann
authors.forename: Hans D
authors.initials: HD
authors.lastname: Lauenstein
authors.forename: Jens
authors.initials: J
authors.lastname: Hohlfeld
authors.forename: Tamara
authors.initials: T
authors.lastname: Becker
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Kaup
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
authors.forename: Sascha
authors.initials: S
authors.lastname: Knauf
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects; D002144:Callithrix; D005260:Female; D008070:Lipopolysaccharides; D008297:Male; D016210:Methacholine Chloride; D010991:Plethysmography; D012129:Respiratory Function Tests
chemical_list: D008070:Lipopolysaccharides; D016210:Methacholine Chloride