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Br J Clin Pharmacol. 2012 Dec;74(6):1023-32. doi: 10.1111/j.1365-2125.2012.04287.x.

Inhaled LPS challenges in smokers: a study of pulmonary and systemic effects.

Author information

1
University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester, Manchester, UK.

Abstract

AIMS:

Lipopolysaccharide (LPS) is a TLR4 agonist which activates NFκB dependent cytokine production. We investigated LPS inhalation in healthy smokers as a model of COPD bacterial exacerbations. We studied safety, reproducibility, the translocation of the NFκB subunit p65 in sputum cells and changes in systemic biomarkers of inflammation.

METHODS:

Twelve smokers inhaled 5 and 30 µg LPS and safety was monitored over 24 h. IL-6, CRP, CCl-18, SP-D, CC-16 and β-defensin 2 were measured in serum samples collected at baseline, 4, 8 and 24 h. Sputum was induced at baseline, 6 and 24 h for cell counts and p65 expression. Repeated challenges were performed after a 2 week interval in 10 smokers.

RESULTS:

LPS inhalation was well tolerated. Significant increases occurred in sputum neutrophil counts with both doses, with a maximum increase of 21.5% at 6 h after 30 µg which was reproducible, r(i ) (intraclass correlation coefficient) = 0.88. LPS increased sputum cell nuclear p65 translocation and phospho-p65 expression. All of the serum biomarkers increased following challenge but with different temporal patterns.

DISCUSSION:

Inhaled LPS challenge in smokers causes pulmonary and systemic inflammation that involves NFκB activation. This appears to be a suitable model for studying bacterial exacerbations of COPD.

PMID:
22469312
PMCID:
PMC3522816
DOI:
10.1111/j.1365-2125.2012.04287.x
[Indexed for MEDLINE]
Free PMC Article
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