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

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.