Reproducibility of the inflammatory response to inhaled endotoxin in healthy volunteers

Kobernick, Aaron K.; Peden, David B.; Zhou, Haibo; Zhou, Qinging; Dillon, Madeline Adams; Alexis, Neil E.

doi:10.1016/j.jaci.2016.04.017

Cited by 3 publications

(1 citation statement)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endotoxin is a strong activator of the innate immune response through its binding to Toll-like receptor 4 on the surface of airway macrophages, inducing a potent pro-inflammatory cytokine response with subsequent recruitment of granulocytes [1]. As both we [3, 4] and others [5] have demonstrated, endotoxin inhalation has both airway and systemic inflammatory effects, with increased neutrophils in induced sputum as well as increased peripheral blood neutrophils. Whether systemic neutrophilia results from airway “spillover” of neutrophils into peripheral blood versus neutrophil recruitment to the blood by systemically release inflammatory cytokines remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Systemic inflammatory response to inhaled endotoxin does not correlate with airway response

et al. 2019

Self Cite

View full text Add to dashboard Cite

BackgroundEndotoxin is a component of particulate matter linked to respiratory disease. Our group has shown that experimental endotoxin inhalation challenge reproducibly triggers neutrophilic inflammation in the airways and in peripheral blood. Sputum induction is currently the only available method for assessing airway neutrophilia but is laborious and time-consuming. This analysis examined the correlation between systemic and airway inflammatory responses to endotoxin to determine if peripheral blood could serve as a surrogate marker for neutrophilic airway inflammation.MethodsWe conducted a retrospective study of 124 inhaled endotoxin challenges conducted at our center using 20,000 endotoxin units (EU) of Clinical Center Reference Endotoxin (CCRE). Venipuncture and induced sputum samples were obtained at baseline and 6 hours after completion of endotoxin challenge. The relationship between change in sputum neutrophils (post-challenge – baseline) and change in peripheral blood neutrophils (post-challenge – baseline) was assessed using Spearman’s correlation analyses.ResultsInhaled endotoxin induced a significant increase in mean sputum percent neutrophils and peripheral blood absolute neutrophil counts in healthy adults with or without mild asthma, but no significant correlation was found between airway and systemic neutrophilia (r = 0.13, p = 0.18). Stratification by degree of airway neutrophil response and by atopic or asthmatic status did not change the results.ConclusionsInhalation challenge with endotoxin safely and effectively induces airway neutrophilic inflammation in most individuals. Increases in endotoxin-induced peripheral blood neutrophils do not correlate well with airway responses and should not be used as a surrogate marker of airway inflammation.

show abstract

Section: Introductionmentioning

confidence: 99%

Systemic inflammatory response to inhaled endotoxin does not correlate with airway response

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

Reply to Shields et al.: Electronic Cigarettes and the Lung Proteome

Tarran

Ghosh

Alexis

2018

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Human lipopolysaccharide models provide mechanistic and therapeutic insights into systemic and pulmonary inflammation

et al. 2020

View full text Add to dashboard Cite

Inflammation is a key feature in the pathogenesis of sepsis and acute respiratory distress syndrome (ARDS). Sepsis and ARDS continue to be associated with high mortality. A key contributory factor is the rudimentary understanding of the early events in pulmonary and systemic inflammation in humans, which are difficult to study in clinical practice, as they precede the patient's presentation to medical services. Lipopolysaccharide (LPS), a constituent of the outer membrane of Gram-negative bacteria, is a trigger of inflammation and the dysregulated host response in sepsis. Human LPS models deliver a small quantity of LPS to healthy volunteers, triggering an inflammatory response and providing a window to study early inflammation in humans. This allows biological/mechanistic insights to be made and new therapeutic strategies to be tested in a controlled, reproducible environment from a defined point in time. We review the use of human LPS models, focusing on the underlying mechanistic insights that have been gained by studying the response to intravenous and pulmonary LPS challenge. We discuss variables that may influence the response to LPS before considering factors that should be considered when designing future human LPS studies.

show abstract

Reproducibility of the inflammatory response to inhaled endotoxin in healthy volunteers

Cited by 3 publications

References 7 publications

Systemic inflammatory response to inhaled endotoxin does not correlate with airway response

Systemic inflammatory response to inhaled endotoxin does not correlate with airway response

Reply to Shields et al.: Electronic Cigarettes and the Lung Proteome

Human lipopolysaccharide models provide mechanistic and therapeutic insights into systemic and pulmonary inflammation

Contact Info

Product

Resources

About