A juvenile murine model with chronic lung inflammation induced by repeated intratracheal instillation of lipopolysaccharides: a versatile and replicable model

Abstract

Background Recurrent lower respiratory tract infection or chronic pulmonary infection often occur in children with chronic lung diseases (CLDs). By continuous lung inflammation, recurrent and chronic infection could cause irreversible airway structural and lung function damage, which eventually leads to respiratory failure and death. Methods In purpose of recapitulating persistent high-intensity lung inflammation caused by recurrent lower respiratory tract infection or chronic infection, we established a juvenile murine model with chronic lung inflammation induced by repeated intratracheal instillations of lipopolysaccharides (LPS) from Pseudomonas aeruginosa once a week for 4 weeks. Four-week-old C57BL/6N mice were divided into 4 groups, including LPS 0.5 group (n=15), LPS 1.0 group (n=15), Control group (n=15) and Normal group (n=15). Mice in LPS 0.5 group and LPS 1.0 group were instilled intratracheally with 0.5 mg/kg LPS and 1.0 mg/kg LPS respectively. Mice in control group were instilled intratracheally with LPS-free sterile 0.9% NaCl, whereas normal group received no treatment. The successful chronic lung inflammation murine model was validated via (I) pathological manifestations of chronic inflammatory mononuclear-cell infiltration and lung parenchyma damage; (II) decreased lung function. Results All mice in LPS 1.0 group died before the third instillation. No death after instillation was observed in Control and LPS 0.5 group. Histological analysis revealed that in LPS 0.5 group, 7 days after the third instillation, most bronchus and parabronchial vessels were wrapped by infiltrating monocytes and lymphocyte and alveolar cavities were compressed, which were not observed in control and normal group. Also, ratio of forced expiratory volume in 0.1 second (FEV 0.1 ) and forced vital capacity (FVC) in LPS 0.5 group was significantly lower (P<0.0001) than both control group and normal group, suggesting ventilatory dysfunction developed after repeatedly intratracheal instillation once a week for 4 weeks. Conclusions Intratracheal instillation of 0.5 mg/kg LPS once a week for 4 weeks can cause chronic lung inflammation in young mice.