Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella pneumoniae in mice.

Abstract:

BACKGROUND: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. METHODS:C57BL/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. RESULTS: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. CONCLUSIONS:Exposure 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.

journal_name

Respir Res

journal_title

Respiratory research

authors

Patterson CM,Morrison RL,D'Souza A,Teng XS,Happel KI

doi

10.1186/1465-9921-13-40

subject

Has Abstract

pub_date

2012-05-31 00:00:00

pages

40

eissn

1465-9921

issn

1465-993X

pii

1465-9921-13-40

journal_volume

13

pub_type

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