Towards clinical applications of anti-endotoxin antibodies; a re-appraisal of the disconnect

Toxins
J C Hurley

Abstract

Endotoxin is a potent mediator of a broad range of patho-physiological effects in humans. It is present in all Gram negative (GN) bacteria. It would be expected that anti-endotoxin therapies, whether antibody based or not, would have an important adjuvant therapeutic role along with antibiotics and other supportive therapies for GN infections. Indeed there is an extensive literature relating to both pre-clinical and clinical studies of anti-endotoxin antibodies. However, the extent of disconnect between the generally successful pre-clinical studies versus the failures of the numerous large clinical trials of antibody based and other anti-endotoxin therapies is under-appreciated and unexplained. Seeking a reconciliation of this disconnect is not an abstract academic question as clinical trials of interventions to reduce levels of endotoxemia levels are ongoing. The aim of this review is to examine new insights into the complex relationship between endotoxemia and sepsis in an attempt to bridge this disconnect. Several new factors to consider in this reappraisal include the frequency and types of GN bacteremia and the underlying mortality risk in the various study populations. For a range of reasons, endotoxemia can no longer be ...Continue Reading

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Citations

Dec 2, 2014·Expert Review of Clinical Immunology·Fernando O Martinez, Siamon Gordon
Jan 21, 2016·Expert Review of Respiratory Medicine·Jordi Rello, Antonio Perez
Feb 13, 2016·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Elizabeth CerceoAlpesh N Amin
Aug 21, 2016·Analytica Chimica Acta·Zeynep AltintasIbtisam E Tothill
Jul 28, 2016·The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine·Simon Nadel
Jun 2, 2016·PloS One·Victoria Martínez-SernándezFlorencio M Ubeira
Mar 18, 2017·Virulence·Rachelle Babb, Liise-Anne Pirofski
Mar 20, 2016·Innate Immunity·Stephan HarmJens Hartmann
Mar 11, 2021·Evolutionary Anthropology·Jessica F Brinkworth, Negin Valizadegan

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Methods Mentioned

BETA
electron microscopy
Assay
PCR

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EUPHAS
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