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

AIMS Lipopolysaccharide (LPS) is a TLR4 agonist which activates NFkB 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 NF kappa B subunit p65 in sputum cells and changes in systemic biomarkers of inflammation. METHODS Twelve smokers inhaled 5 and 30 mg LPS and safety was monitored over 24 h. IL-6, CRP, CCl-18, SP-D, CC-16 and beta-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 mg 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 NFkB activation. This appears to be a suitable model for studying bacterial exacerbations of COPD.