Polymorphonuclear neutrophils are thought to play a critical role in the pathogenesis of respiratory conditions in diseases such as chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis. Charles River conducts contract studies in a rodent model of acute pulmonary neutrophilia, which has been extensively characterized and used as a preclinical surrogate tool to examine the condition in small animals.
Acute lung neutrophilia is induced by exposing a rat model to a pulmonary airway challenge of lipopolysaccharide (LPS), which is known to be a significant and active component of cigarette smoke, the leading cause of COPD. The condition attains significance within 4 hours, peaks around 8 hours, and then remains elevated for up to 12 hours. Pretreatment with glucocorticoids, such as betamethasone, has demonstrated a dose-dependent decrease in neutrophil count. Orally-administered betamethasone, at 0.03, 0.3 and 3 mg/kg 2 hours prior to LPS challenge, results in a dose-dependent inhibition of neutrophils, attaining > 80% inhibition at 3.0 mg/kg at both 4 and 24 hours after challenge, compared to animals that receive saline alone.
Additional services that can be combined with this model include cytokine profiling, histopathologic evaluations and assessments of airway hyperresponsiveness (e.g., Penh assessments in conscious animals or anesthetized assessments of resistance and compliance).
Testing / Validation Data
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