Characterization of the inflammatory response to inhaled lipopolysaccharide in mild to moderate chronic obstructive pulmonary disease

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 FEV₁ 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.

DOI: 10.1111/bcp.12546

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