Characterization of the inflammatory response to inhaled lipopolysaccharide in mild to moderate chronic obstructive pulmonary disease.
OBJECTIVE
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.
Medicines Evaluation Unit, University Hospital of South Manchester Foundation Trust, University of Manchester, Southmoor Rd, Manchester, UK.
Vandana
V
Gupta
Antonia
A
Banyard
Aoibheann
A
Mullan
Srividya
S
Sriskantharajah
Thomas
T
Southworth
Dave
D
Singh
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002452:Cell Count; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology / Q000276:immunology
D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D008070:Lipopolysaccharides
COPD; COPD exacerbations; IL-17; lipopolysaccharide; sputum neutrophils