Experimental pulmonary infection and colonization of Haemophilus influenzae in emphysematous hamsters

Abstract

Background: Bacterial infection has been considered the main cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, experimental model of COPD exacerbation induced by Haemophilus influenzae infection was not available up to now. Furthermore, only a few studies on evaluation of antibiotics using an H. influenzae infection model in mice have been reported. The aim of this work was to evaluate the activity of moxifloxacin on experimental pulmonary infection and colonization of H. influenzae in emphysematous hamsters.

Methods: Pulmonary emphysema was developed by intratracheal instillation of porcine pancreatic elastase in golden hamsters, which were infected by agar-beads enclosing H. influenzae to establish animal models of AECOPD. Alterations of lung histopathology, inflammatory factor levels in plasma and bronchoalveolar lavage fluids (BALFs), viable cell counting of lung tissue were determined on different days after challenge and moxifloxacin administration.

Results: Lung bacterial counts of BALFs and homogenates were significantly higher in emphysematous hamsters than those in normal non-emphysematous animals from 1 to 3 weeks after intratracheal inoculation of bacterial agar-beads suspensions. Moreover, H. influenzae colonized and survived for a longer period of time in emphysematous lungs than in normal non-emphysematous lungs after challenge. Efficacy of 3-day intragastric administration of moxifloxacin was proved by reduction in pulmonary H. influenzae burden and alleviation of inflammatory responses on days 4, 8 and 21 post-inoculation. No planktonic bacteria were isolated from BALFs in the first week after moxifloxacin treatment, and bacterial load in lung tissue homogenates declined significantly. Nevertheless, after 3 weeks, bacterial load in BALFs and homogenates of emphysematous lungs recovered to a large quantity. Inflammation in lung tissue, including lung consolidation, hemorrhage, and neutrophils infiltration, was conspicuously improved after administration of moxifloxacin. Levels of inflammatory factors in plasma were significantly decreased on days 8 and 21 after treatment compared with that without drug therapy. Inflammatory factors in BALF were also reduced, among which IL-8 dropped down markedly in early stage.

Conclusion: Our results suggest that chronic bacterial infection and colonization is highly correlated with lung emphysematous lesions, which would be one of the important mechanisms for repeated attacks of acute exacerbations of chronic pulmonary diseases and uncertain efficacies of antibiotics.