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Characterization of the inflammatory response to inhaled lipopolysaccharide in mild to moderate chronic obstructive pulmonary disease
Author(s) -
Gupta Vandana,
Banyard Antonia,
Mullan Aoibheann,
Sriskantharajah Srividya,
Southworth Thomas,
Singh Dave
Publication year - 2015
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12546
Subject(s) - medicine , copd , systemic inflammation , sputum , inhalation , neutrophil elastase , inflammation , immunology , peripheral blood mononuclear cell , lipopolysaccharide , c reactive protein , lipopolysaccharide binding protein , acute phase protein , pathology , anesthesia , biology , tuberculosis , biochemistry , in vitro
Aims Lipopolysaccharide ( LPS ) inhalation causes increased airway and systemic inflammation. We investigated LPS inhalation in patients with chronic obstructive pulmonary disease ( COPD ) as a model of bacterial exacerbations. We studied safety, changes in sputum and systemic biomarkers. We have also investigated interleukin ( IL )‐17 concentrations in this model. Methods Twelve COPD patients inhaled 5 μg LPS . Safety was monitored over 24 h. Sputum was induced at baseline, 6 and 24 h for cells and IL ‐8, IL ‐17, neutrophil elastase, monocyte chemoattractant protein‐1 ( MCP ‐1) and macrophage inflammatory protein‐1β ( MIP ‐1β) in supernatants. Serum was collected at baseline, 4, 8 and 24 h for IL ‐6, C‐reactive protein ( CRP ) and Clara cell protein ( CC ‐16) concentrations. Peripheral blood mononuclear cells ( PBMCs ) were isolated at baseline and 4 h for systemic IL ‐17 analysis. Results LPS 5 μg was well tolerated. The greatest FEV 1 change was 11.7% (mean) at 1 h (95% CI 5.1–18.2%). There was a large range in maximal fall (2.5–37.7%). Total sputum cell count and neutrophil count significantly increased 6 and 24 h post‐ LPS . There was no change in sputum supernatant mediators. IL ‐6, CRP and CC ‐16 increased post‐inhalation, with different temporal patterns. CD4+ and CD8+ cell associated IL ‐17 significantly increased at 4 h. Conclusions Inhaled LPS in COPD patients safely causes increased airway and systemic inflammation. This may be a model for studying COPD exacerbations.