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.
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 COPDpatients 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 COPDpatients safely causes increased airway and systemic inflammation. This may be a model for studying COPD exacerbations.
Authors: Nico A Maris; Alex F de Vos; Mark C Dessing; C Arnold Spek; Rene Lutter; Henk M Jansen; Jaring S van der Zee; Paul Bresser; Tom van der Poll Journal: Am J Respir Crit Care Med Date: 2005-06-30 Impact factor: 21.405
Authors: A Blomberg; I Mudway; M Svensson; A Hagenbjörk-Gustafsson; L Thomasson; R Helleday; X Dumont; B Forsberg; G Nordberg; A Bernard Journal: Eur Respir J Date: 2003-12 Impact factor: 16.671
Authors: Johann Bartko; Leopold Stiebellehner; Ulla Derhaschnig; Christian Schoergenhofer; Michael Schwameis; Helmut Prosch; Bernd Jilma Journal: Br J Clin Pharmacol Date: 2016-01-15 Impact factor: 4.335
Authors: J Bartko; C Schoergenhofer; M Schwameis; N Buchtele; J Wojta; G Schabbauer; L Stiebellehner; B Jilma Journal: J Thromb Haemost Date: 2016-10-24 Impact factor: 5.824
Authors: Dave Singh; Leonard Siew; Jared Christensen; Jonathan Plumb; Graham W Clarke; Steve Greenaway; Christelle Perros-Huguet; Nick Clarke; Iain Kilty; Lisa Tan Journal: Eur J Clin Pharmacol Date: 2015-08-13 Impact factor: 3.064