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Inhalation of LPS induces inflammatory airway responses mimicking characteristics of chronic obstructive pulmonary disease
Author(s) -
Korsgren Magnus,
Linden Margareta,
Entwistle Neil,
Cook Jason,
Wollmer Per,
Andersson Morgan,
Larsson Bengt,
Greiff Lennart
Publication year - 2012
Publication title -
clinical physiology and functional imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.608
H-Index - 67
eISSN - 1475-097X
pISSN - 1475-0961
DOI - 10.1111/j.1475-097x.2011.01058.x
Subject(s) - medicine , sputum , copd , inhalation , neutrophil elastase , inflammation , immunology , desmosine , lipopolysaccharide , bronchoalveolar lavage , lung , pathology , anesthesia , elastin , tuberculosis
Summary 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.