Increase in proinflammatory cytokines in peripheral blood without haemostatic changes after LPS inhalation

Fouassier, Marc; Souweine, Bertrand; Sapin, Anne‐Françoise; Hashemzadeh, Afshin; Marquès-Verdier, Alain; Caillaud, D.

doi:10.1016/j.thromres.2009.06.014

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…Inhaled LPS increased serum IL-6 and CRP in COPD patients. This has also been observed in healthy volunteers [6,8,9]. IL-6 regulates CRP production by the liver [38], explaining the temporal difference in the increase in these biomarkers.…”

Section: Discussionsupporting

confidence: 62%

“…Lipopolysaccharide (LPS), also known as endotoxin, is a constituent of the outer cell membrane of gram negative bacteria and triggers an innate immune response after binding to Toll like receptor 4 (TLR4) . Inhaled LPS has been used experimentally in healthy subjects and patients with asthma to cause acute neutrophilic airway inflammation , which is accompanied by a short lived systemic immune response involving an increase in C‐reactive protein (CRP) and interleukin 6 (IL‐6) concentrations . This model has been used safely in healthy subjects in order to investigate the effects of anti‐inflammatory drugs on neutrophilic airway inflammation .…”

Section: Introductionmentioning

confidence: 99%

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

Gupta

Banyard

Mullan

et al. 2015

Brit J Clinical Pharma

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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. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Inhaled lipopolysaccharide (LPS) has been used safely in healthy subjects, asthmatics and smokers to induce increased neutrophilic inflammation and to assess the effects of novel drugs. • Chronic obstructive pulmonary disease (COPD) exacerbations are characterized by increased neutrophilic inflammation. WHAT THIS STUDY ADDS • We performed LPS inhalation safely in 12 COPD patients. • Inhaled LPS in COPD patients increased airway and systemic inflammation; this appears to be a model that resembles COPD exacerbations and could be used to evaluate novel COPD therapies.

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Section: Discussionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

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

Gupta

Banyard

Mullan

et al. 2015

Brit J Clinical Pharma

View full text Add to dashboard Cite

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Respiratory toxicity biomarkers

Kodavanti¹

2014

Biomarkers in Toxicology

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Lipopolysaccharide challenge: immunological effects and safety in humans

Zielen

Trischler

Schubert

2015

Expert Review of Clinical Immunology

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Lipopolysaccharide (LPS) is a constituent of the outer membranes of Gram-negative bacteria and an important microbial trigger that stimulates innate immunity. It is ubiquitous; it can be inoculated from the environment via inhalation of dust. The resultant inflammatory responses are essential to early host defense but may also contribute to later and/or chronic organ injury. LPS challenge either intravenously or by inhalation has been widely used for the evaluation of anti-inflammatory reagents as well as to address basic scientific questions. The acute inhalation of LPS is used as a model of acute bronchitis in human volunteers. LPS inhalation is considered a well-established method that is safe and tolerable and aids in the improved characterization of anti-inflammatory drugs in proof-of-concept studies. This article reviews immunogenicity and safety data pertaining to LPS administration, with a particular focus on LPS inhalation, which may facilitate the optimization of its use in human research.

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Increase in proinflammatory cytokines in peripheral blood without haemostatic changes after LPS inhalation

Cited by 3 publications

References 40 publications

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

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

Respiratory toxicity biomarkers

Lipopolysaccharide challenge: immunological effects and safety in humans

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