Chronic Obstructive Pulmonary Disease (COPD) Model 

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 Discovery Research Services (DRS) offers an acute rodent model of pulmonary neutrophilia, the rat lipopolysaccharide (LPS) model, which has been extensively characterized and used as a preclinical surrogate tool to examine pulmonary neutrophilia in small animals.

In this COPD model, acute lung neutrophilia is induced by exposing animals to a pulmonary airway challenge of LPS, which is known to be a significant and active component of cigarette smoke, the leading cause of COPD. Sprague Dawley® rats are exposed to a single inhaled LPS challenge, resulting in an acute pulmonary neutrophilia, which attains significance within 4 hours, peaking around 8 hours, and 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.