Host defences against metabolic endotoxaemia and their impact on lipopolysaccharide detection

Faraj, Tola and McLaughlin, Catherine and Erridge, Clett (2017) Host defences against metabolic endotoxaemia and their impact on lipopolysaccharide detection. International Reviews of Immunology. ISSN 1563-5244

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Official URL: http://www.tandfonline.com/doi/full/10.1080/088301...

Abstract

Bacterial endotoxin (lipopolysaccharide, LPS), is one of the most potent inducers of inflammatory signalling, yet it is abundant in the human gut and the modern diet. Small quantities of LPS routinely translocate from the gut lumen to the circulation (so-called ‘metabolic endotoxaemia’), and elevated plasma LPS concentrations are reported in a variety of chronic non-communicable diseases, including obesity, non-alcoholic fatty liver disease, atherosclerosis and type II diabetes. Murine models of experimentally-induced endotoxaemia and Toll-like receptor-4 deficiency suggest that endotoxin may promote the metabolic disturbances that underpin these diseases. However, as bioactive LPS is cleared rapidly from the circulation, and reported levels of endotoxin in human plasma vary widely, the potential relevance of metabolic endotoxaemia to human disease remains unclear. We here review insight into these questions gained from human and murine models of experimental endotoxaemia, focussing on the kinetics of LPS neutralisation and its clearance from blood, the limitations of the widely used limulus assay and alternative methods for LPS quantitation. We conclude that although new methods for LPS measurement will be required to definitively quantify the extent of metabolic endotoxaemia in man, evidence from numerous approaches suggests that this molecule may play a key role in the development of diverse metabolic diseases.

Item Type: Journal Article
Keywords: atherosclerosis, endotoxin, metabolism
Faculty: Faculty of Science & Technology
Depositing User: Dr Clett Erridge
Date Deposited: 23 Jan 2017 16:52
Last Modified: 09 Aug 2017 09:52
URI: http://arro.anglia.ac.uk/id/eprint/701419

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