Abstract
Chronic Obstructive Pulmonary Disease (COPD) is a complex respiratory disease and is a major cause of morbidity and mortality in adults in developed countries. The presence of pathogens such as Haemophilus influenzae and S. pneumoniae in the lower airways of COPD sufferers has been associated with an increase in exacerbation frequency. Recently, a new model of chronic pulmonary pneumococcal infection has been described in mice, which mimics the low-level colonisation observed in a large proportion of COPD sufferers. The aim of this study was to better understand the effect of an acute model of LPS challenge on a chronic pneumococcal infection. Intranasal administration of LPS, induces neutrophilia which is another hallmark of COPD and has historically been used to mimic COPD phenotypes in mice.
Inbred mice were intranasally challenged with S. pneumoniae and 14 days post-infection mice were intranasally challenged with LPS and culled 6 hours post-challenge. An acute LPS challenge to mice with a chronic pneumococcal infection resulted in an increase of neutrophils in the BALF compared to mice challenged with LPS or pneumococcal infection alone (p < 0.005). The cytokine keratinocyte chemoattractant was significantly raised in the BALF of mice that received LPS (p < 0.01) regardless of whether pneumococci were present. IL-12p40 was significantly raised (p < 0.05) in mice that received both challenges compared to mice that received either challenge in isolation. Intranasal LPS challenge in combination with chronic infection resulted in a worsening of disease signs, which could mimic a COPD exacerbation.
- © 2014 ERS