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Inhalation of LPS induces inflammatory airway responses mimicking characteristics of chronic obstructive pulmonary disease.

Korsgren, Magnus LU ; Linden, Margareta ; Entwistle, Neil ; Cook, Jason ; Wollmer, Per LU ; Andersson, Morgan LU ; Larsson, Bengt LU and Greiff, Lennart (2012) In Clinical Physiology and Functional Imaging 32(1). p.71-79
Abstract
Aim: Inhalation of lipopolysaccharide (LPS) produces both systemic and pulmonary inflammatory responses. The aim of this study was to further characterize the response to LPS in order to develop a human model suitable for early testing of drug candidates developed for the treatment for chronic obstructive pulmonary disease (COPD). Materials: Blood and induced sputum were obtained 4, 24 and 48 h following inhalation of saline and LPS (5 and 50 μg). Blood was analysed for C-reactive protein (CRP), α(1) -antitrypsin and neutrophils/leucocytes, and sputum was analysed for biomarkers of neutrophil inflammation and remodelling activities, i.e. neutrophil elastase (NE) protein/activity and α(1) -antitrypsin. Levels of tumour necrosis factor-α... (More)
Aim: Inhalation of lipopolysaccharide (LPS) produces both systemic and pulmonary inflammatory responses. The aim of this study was to further characterize the response to LPS in order to develop a human model suitable for early testing of drug candidates developed for the treatment for chronic obstructive pulmonary disease (COPD). Materials: Blood and induced sputum were obtained 4, 24 and 48 h following inhalation of saline and LPS (5 and 50 μg). Blood was analysed for C-reactive protein (CRP), α(1) -antitrypsin and neutrophils/leucocytes, and sputum was analysed for biomarkers of neutrophil inflammation and remodelling activities, i.e. neutrophil elastase (NE) protein/activity and α(1) -antitrypsin. Levels of tumour necrosis factor-α (TNFα) were measured in both blood and sputum. Urine was collected 0-24 and 24-48 h postchallenge, and desmosine, a biomarker of elastin degradation, was measured. Results: Lipopolysaccharide inhalation induced dose-dependent flu-like symptoms and increases in plasma CRP and α(1) -antitrypsin as well as increases in blood neutrophil/leucocyte numbers. Furthermore, LPS produced increases in sputum TNFα and sputum NE activity. Urine levels of desmosine were unaffected by the LPS challenge. All subjects recovered 48 h postchallenge, and indices of inflammatory activity were significantly lower at this observation point cf 24 h postchallenge. Conclusion: Inhalation of LPS in healthy volunteers can be used as a safe and stable model of neutrophil inflammation. Blood/plasma and sputum indices can be employed to monitor the response to LPS. We suggest that this model may be used for initial human studies of novel COPD-active drugs. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Physiology and Functional Imaging
volume
32
issue
1
pages
71 - 79
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000297928900012
  • pmid:22152082
  • scopus:83555174551
  • pmid:22152082
ISSN
1475-0961
DOI
10.1111/j.1475-097X.2011.01058.x
language
English
LU publication?
yes
id
50b45e76-30ec-4b75-bf44-ee8618ae43ef (old id 2274264)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22152082?dopt=Abstract
date added to LUP
2016-04-04 08:56:58
date last changed
2023-09-05 18:38:58
@article{50b45e76-30ec-4b75-bf44-ee8618ae43ef,
  abstract     = {{Aim: Inhalation of lipopolysaccharide (LPS) produces both systemic and pulmonary inflammatory responses. The aim of this study was to further characterize the response to LPS in order to develop a human model suitable for early testing of drug candidates developed for the treatment for chronic obstructive pulmonary disease (COPD). Materials: Blood and induced sputum were obtained 4, 24 and 48 h following inhalation of saline and LPS (5 and 50 μg). Blood was analysed for C-reactive protein (CRP), α(1) -antitrypsin and neutrophils/leucocytes, and sputum was analysed for biomarkers of neutrophil inflammation and remodelling activities, i.e. neutrophil elastase (NE) protein/activity and α(1) -antitrypsin. Levels of tumour necrosis factor-α (TNFα) were measured in both blood and sputum. Urine was collected 0-24 and 24-48 h postchallenge, and desmosine, a biomarker of elastin degradation, was measured. Results: Lipopolysaccharide inhalation induced dose-dependent flu-like symptoms and increases in plasma CRP and α(1) -antitrypsin as well as increases in blood neutrophil/leucocyte numbers. Furthermore, LPS produced increases in sputum TNFα and sputum NE activity. Urine levels of desmosine were unaffected by the LPS challenge. All subjects recovered 48 h postchallenge, and indices of inflammatory activity were significantly lower at this observation point cf 24 h postchallenge. Conclusion: Inhalation of LPS in healthy volunteers can be used as a safe and stable model of neutrophil inflammation. Blood/plasma and sputum indices can be employed to monitor the response to LPS. We suggest that this model may be used for initial human studies of novel COPD-active drugs.}},
  author       = {{Korsgren, Magnus and Linden, Margareta and Entwistle, Neil and Cook, Jason and Wollmer, Per and Andersson, Morgan and Larsson, Bengt and Greiff, Lennart}},
  issn         = {{1475-0961}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{71--79}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Clinical Physiology and Functional Imaging}},
  title        = {{Inhalation of LPS induces inflammatory airway responses mimicking characteristics of chronic obstructive pulmonary disease.}},
  url          = {{http://dx.doi.org/10.1111/j.1475-097X.2011.01058.x}},
  doi          = {{10.1111/j.1475-097X.2011.01058.x}},
  volume       = {{32}},
  year         = {{2012}},
}