Inhalation of LPS induces inflammatory airway responses mimicking characteristics of chronic obstructive pulmonary disease.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2274264
- author
- Korsgren, Magnus LU ; Linden, Margareta ; Entwistle, Neil ; Cook, Jason ; Wollmer, Per LU ; Andersson, Morgan LU ; Larsson, Bengt LU and Greiff, Lennart
- organization
- publishing date
- 2012
- 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}}, }