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

Lookup NU author(s): Daniel Brooks, Dr Sarah Wiscombe, Professor John Simpson, Dr Anthony Rostron

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Abstract

Copyright ©ERS 2020.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, focussing 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.


Publication metadata

Author(s): Brooks D, Barr LC, Wiscombe S, McAuley DF, Simpson AJ, Rostron AJ

Publication type: Review

Publication status: Published

Journal: The European Respiratory Journal

Year: 2020

Volume: 56

Issue: 1

Online publication date: 30/07/2020

Acceptance date: 18/03/2020

ISSN (print): 0903-1936

ISSN (electronic): 1399-3003

Publisher: NLM (Medline)

URL: https://doi.org/10.1183/13993003.01298-2019

DOI: 10.1183/13993003.01298-2019

PubMed id: 32299854


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