Inhaled fluticasone propionate impairs pulmonary clearance of <it>Klebsiella Pneumoniae</it> in mice
<p>Abstract</p> <p>Background</p> <p>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 defen...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-05-01
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| Series: | Respiratory Research |
| Online Access: | http://respiratory-research.com/content/13/1/40 |
| _version_ | 1811265318766510080 |
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| author | Patterson Craig M Morrison Richard L D’Souza Alain Teng Xu S Happel Kyle I |
| author_facet | Patterson Craig M Morrison Richard L D’Souza Alain Teng Xu S Happel Kyle I |
| author_sort | Patterson Craig M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>C57BL/6 mice received daily, nose-only exposure to nebulized FP or vehicle for 8 days, followed by pulmonary challenge with <it>Klebsiella pneumoniae</it>. Bacterial burden, phagocytosis, leukocyte recruitment, cytokine expression, nitric oxide release, and survival were measured.</p> <p>Results</p> <p>Inhaled 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.</p> <p>Conclusions</p> <p>Exposure to inhaled FP impairs pulmonary clearance of <it>K. pneumoniae</it> 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.</p> |
| first_indexed | 2024-04-12T20:21:30Z |
| format | Article |
| id | doaj.art-7560640e00c34eea870f83c895115279 |
| institution | Directory Open Access Journal |
| issn | 1465-9921 |
| language | English |
| last_indexed | 2024-04-12T20:21:30Z |
| publishDate | 2012-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-7560640e00c34eea870f83c8951152792022-12-22T03:17:59ZengBMCRespiratory Research1465-99212012-05-011314010.1186/1465-9921-13-40Inhaled fluticasone propionate impairs pulmonary clearance of <it>Klebsiella Pneumoniae</it> in micePatterson Craig MMorrison Richard LD’Souza AlainTeng Xu SHappel Kyle I<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>C57BL/6 mice received daily, nose-only exposure to nebulized FP or vehicle for 8 days, followed by pulmonary challenge with <it>Klebsiella pneumoniae</it>. Bacterial burden, phagocytosis, leukocyte recruitment, cytokine expression, nitric oxide release, and survival were measured.</p> <p>Results</p> <p>Inhaled 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.</p> <p>Conclusions</p> <p>Exposure to inhaled FP impairs pulmonary clearance of <it>K. pneumoniae</it> 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.</p>http://respiratory-research.com/content/13/1/40 |
| spellingShingle | Patterson Craig M Morrison Richard L D’Souza Alain Teng Xu S Happel Kyle I Inhaled fluticasone propionate impairs pulmonary clearance of <it>Klebsiella Pneumoniae</it> in mice Respiratory Research |
| title | Inhaled fluticasone propionate impairs pulmonary clearance of <it>Klebsiella Pneumoniae</it> in mice |
| title_full | Inhaled fluticasone propionate impairs pulmonary clearance of <it>Klebsiella Pneumoniae</it> in mice |
| title_fullStr | Inhaled fluticasone propionate impairs pulmonary clearance of <it>Klebsiella Pneumoniae</it> in mice |
| title_full_unstemmed | Inhaled fluticasone propionate impairs pulmonary clearance of <it>Klebsiella Pneumoniae</it> in mice |
| title_short | Inhaled fluticasone propionate impairs pulmonary clearance of <it>Klebsiella Pneumoniae</it> in mice |
| title_sort | inhaled fluticasone propionate impairs pulmonary clearance of it klebsiella pneumoniae it in mice |
| url | http://respiratory-research.com/content/13/1/40 |
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