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

Raminder Aul, Jane Armstrong, Annelyse Duvoix, David Lomas, Brian Hayes, Bruce E. Miller, Chris Jagger, Dave Singh

    Research output: Contribution to journalArticlepeer-review

    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 30μg LPS and safety was monitored over 24h. IL-6, CRP, CCl-18, SP-D, CC-16 and β-defensin 2 were measured in serum samples collected at baseline, 4, 8 and 24h. Sputum was induced at baseline, 6 and 24h for cell counts and p65 expression. Repeated challenges were performed after a 2week 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 6h after 30μg which was reproducible, ri (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. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
    Original languageEnglish
    Pages (from-to)1023-1032
    Number of pages9
    JournalBritish Journal of Clinical Pharmacology
    Volume74
    Issue number6
    DOIs
    Publication statusPublished - Dec 2012

    Keywords

    • Induced sputum
    • Lipopolysaccharide
    • Smoker

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