Roflumilast increases bacterial load and dissemination in a model of Pseudomononas aeruginosa airway infection
Kasetty, Gopinath LU ; Papareddy, Praveen LU
; Bhongir, Ravi
LU
and Egesten, Arne
LU
(2016)
In Journal of Pharmacology and Experimental Therapeutics
357(1).
p.66-72
- Abstract
- Exacerbations present a major clinical problem in many patients suffering from COPD. Roflumilast, an inhibitor of phosphodiesterase 4, has beneficial effects in several clinical trials and is currently widely used to prevent exacerbations in severe COPD. Roflumilast has anti-inflammatory properties that may interfere with potentially important host defense functions, including cytotoxic properties of neutrophils at sites of inflammation. Since chronic bacterial infection are prevalent in severe COPD, Pseudomonas aeruginosa being a major pathogen, we hypothesized that this drug could impair host defense against P. aeruginosa. In this study, mice were pretreated with vehicle alone or roflumilast at doses of 5 mg/kg or 10 mg/kg followed by... (More)
- Exacerbations present a major clinical problem in many patients suffering from COPD. Roflumilast, an inhibitor of phosphodiesterase 4, has beneficial effects in several clinical trials and is currently widely used to prevent exacerbations in severe COPD. Roflumilast has anti-inflammatory properties that may interfere with potentially important host defense functions, including cytotoxic properties of neutrophils at sites of inflammation. Since chronic bacterial infection are prevalent in severe COPD, Pseudomonas aeruginosa being a major pathogen, we hypothesized that this drug could impair host defense against P. aeruginosa. In this study, mice were pretreated with vehicle alone or roflumilast at doses of 5 mg/kg or 10 mg/kg followed by instillation of P. aeruginosa in the airways. Bacterial load and dissemination as well as inflammatory markers and immune cells present in the airways were followed. Roflumilast increased mortality, bacterial load and dissemination in mice infected with P. aeruginosa. In addition, roflumilast-treated mice had significantly lower number of neutrophils in the bronchi but not in the lung tissue airways compared with untreated mice. Several proinflammatory cytokines decreased in roflumilast-treated mice but neither the neutrophil-recruiting chemokine KC nor IL-6. The findings show that roflumilast-treatment impair host defense against P. aeruginosa in the airways. This may imply that patients suffering from chronic bacterial infection of the airways could benefit from being withheld treatment with roflumilast. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8825772
- author
- Kasetty, Gopinath
LU
; Papareddy, Praveen
LU
; Bhongir, Ravi
LU
and Egesten, Arne
LU
- organization
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Pharmacology and Experimental Therapeutics
- volume
- 357
- issue
- 1
- pages
- 66 - 72
- publisher
- American Society for Pharmacology and Experimental Therapeutics
- external identifiers
-
- pmid:26865680
- wos:000372142800008
- scopus:84962524526
- pmid:26865680
- ISSN
- 1521-0103
- DOI
- 10.1124/jpet.115.229641
- language
- English
- LU publication?
- yes
- id
- 2b524402-3b78-4215-9f6d-a737502e21e7 (old id 8825772)
- alternative location
- https://www.ncbi.nlm.nih.gov/pubmed/26865680
- date added to LUP
- 2016-04-04 09:25:24
- date last changed
- 2022-04-23 20:29:10
@article{2b524402-3b78-4215-9f6d-a737502e21e7,
abstract = {{Exacerbations present a major clinical problem in many patients suffering from COPD. Roflumilast, an inhibitor of phosphodiesterase 4, has beneficial effects in several clinical trials and is currently widely used to prevent exacerbations in severe COPD. Roflumilast has anti-inflammatory properties that may interfere with potentially important host defense functions, including cytotoxic properties of neutrophils at sites of inflammation. Since chronic bacterial infection are prevalent in severe COPD, Pseudomonas aeruginosa being a major pathogen, we hypothesized that this drug could impair host defense against P. aeruginosa. In this study, mice were pretreated with vehicle alone or roflumilast at doses of 5 mg/kg or 10 mg/kg followed by instillation of P. aeruginosa in the airways. Bacterial load and dissemination as well as inflammatory markers and immune cells present in the airways were followed. Roflumilast increased mortality, bacterial load and dissemination in mice infected with P. aeruginosa. In addition, roflumilast-treated mice had significantly lower number of neutrophils in the bronchi but not in the lung tissue airways compared with untreated mice. Several proinflammatory cytokines decreased in roflumilast-treated mice but neither the neutrophil-recruiting chemokine KC nor IL-6. The findings show that roflumilast-treatment impair host defense against P. aeruginosa in the airways. This may imply that patients suffering from chronic bacterial infection of the airways could benefit from being withheld treatment with roflumilast.}},
author = {{Kasetty, Gopinath and Papareddy, Praveen and Bhongir, Ravi and Egesten, Arne}},
issn = {{1521-0103}},
language = {{eng}},
number = {{1}},
pages = {{66--72}},
publisher = {{American Society for Pharmacology and Experimental Therapeutics}},
series = {{Journal of Pharmacology and Experimental Therapeutics}},
title = {{Roflumilast increases bacterial load and dissemination in a model of <i>Pseudomononas aeruginosa</i> airway infection}},
url = {{http://dx.doi.org/10.1124/jpet.115.229641}},
doi = {{10.1124/jpet.115.229641}},
volume = {{357}},
year = {{2016}},
}