Abstract
BackgroundRecent trials demonstrate increased pneumonia risk in chronic obstructive pulmonary disease patients treated with the inhaled corticosteroid (ICS) fluticasone propionate (FP). There is limited work describing FP effects on host defenses against bacterial pneumonia.MethodsC57BL/6 mice received daily, nose-only exposure to nebulized FP or vehicle for 8 days, followed by pulmonary challenge with Klebsiella pneumoniae. Bacterial burden, phagocytosis, leukocyte recruitment, cytokine expression, nitric oxide release, and survival were measured.ResultsInhaled FP increased bacterial burden in lungs and blood 48 h after infection but affected neither in vivo phagocytosis of bacteria by alveolar macrophages (AM) nor alveolar neutrophil recruitment. AM from FP-treated mice showed impaired expression of infection induced TNF-alpha, IP-10 (CXCL-10), and interleukin 6 (IL-6), and AM also showed a trend towards impaired intracellular pathogen control following in vivo infection. In vitro FP treatment resulted in a dose-dependent impairment of cytokine expression by AM. Furthermore, infection-induced nitric oxide (but not hydrogen peroxide) production was impaired by FP in vivo and in vitro. FP decreased survival in this model.ConclusionsExposure to inhaled FP impairs pulmonary clearance of K. pneumoniae in mice, an effect associated with greater systemic bacteremia and death. Decreased AM cytokine and nitric oxide expression parallel the failure to control infection. These results support the study of ICS effects on human pulmonary host defenses.
Highlights
The immune modulatory effects of inhaled corticosteroids (ICS) on inflammatory airway diseases are wellrecognized, and they are widely used in the treatment of asthma [1]
Histologic examination of lung tissues at 24 hours post-infection revealed only small areas of peribronchial neutrophil influx in control animals (Figure 2A), whereas lungs from fluticasone propionate (FP)-treated mice showed frequent and larger areas of confluent consolidation within the lung parenchyma (Figure 2B)
We conducted experiments to test the effects of inhaled FP on the in vivo phagocytosis of K. pneumoniae by mouse alveolar macrophages
Summary
The immune modulatory effects of inhaled corticosteroids (ICS) on inflammatory airway diseases are wellrecognized, and they are widely used in the treatment of asthma [1]. Several large, randomized trials have demonstrated significant clinical benefits of ICS, such as fewer acute COPD exacerbations, better lung function, and improved symptom scores [3,4,5]. Despite these benefits, multiple trials have revealed an increased incidence of pneumonia diagnosis in COPD patients given ICS, The effects of glucocorticoids (both systemic and inhaled) on airways inflammation are well-documented and have led to the widespread use of these medications in the treatment of obstructive lung diseases. Recent trials demonstrate increased pneumonia risk in chronic obstructive pulmonary disease patients treated with the inhaled corticosteroid (ICS) fluticasone propionate (FP). There is limited work describing FP effects on host defenses against bacterial pneumonia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
