TY - JOUR T1 - Human lipopolysaccharide models provide mechanistic and therapeutic insights into systemic and pulmonary inflammation JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01298-2019 VL - 56 IS - 1 SP - 1901298 AU - Daniel Brooks AU - Laura C. Barr AU - Sarah Wiscombe AU - Daniel F. McAuley AU - A. John Simpson AU - Anthony J. Rostron Y1 - 2020/07/01 UR - http://erj.ersjournals.com/content/56/1/1901298.abstract N2 - 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.Human lipopolysaccharide challenge models are a useful adjunct to clinical studies in refining understanding of the host innate immune response to help identify therapeutic targets in an attempt to improve outcomes in critical illness https://bit.ly/3aiCmrx ER -