Next Article in Journal
Venom Down Under: Dynamic Evolution of Australian Elapid Snake Toxins
Next Article in Special Issue
Active Immunity Induced by Passive IgG Post-Exposure Protection against Ricin
Previous Article in Journal
Expression of VEGF and Flk-1 and Flt-1 Receptors during Blood-Brain Barrier (BBB) Impairment Following Phoneutria nigriventer Spider Venom Exposure
Previous Article in Special Issue
Cloning and Characterization of a Hybridoma Secreting a 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-Specific Monoclonal Antibody and Recombinant F(ab)
A comment was published on 11 April 2014, see Toxins 2014, 6(4), 1362-1363.

Toxins 2013, 5(12), 2589-2620; doi:10.3390/toxins5122589
Review

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

1,2,3
1 Rural Health Academic Center, Melbourne Medical School, University of Melbourne, Parkville 3010, Australia 2 Division of Internal Medicine, Ballarat Health Services, Ballarat 3350, Australia 3 Infection Control Committees, St John of God Hospital and Ballarat Health Services, Ballarat 3353, Australia 
Received: 31 October 2013 / Revised: 9 December 2013 / Accepted: 13 December 2013 / Published: 18 December 2013
(This article belongs to the Special Issue Toxin-Antibody Interactions)
View Full-Text   |   Download PDF [462 KB, uploaded 18 December 2013]   |   Browse Figures

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 considered as a single entity. There are old clinical trials which warrant a re-appraisal in light of these recent advances in the understanding of the structure-function relationship of endotoxin. Fundamentally however, the disconnect not only remains, it has enlarged.
Keywords: endotoxin; endotoxemia; anti-endotoxin antibodies; sepsis; polymyxin; Gram-negative bacteria endotoxin; endotoxemia; anti-endotoxin antibodies; sepsis; polymyxin; Gram-negative bacteria
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote
MDPI and ACS Style

Hurley, J.C. Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect. Toxins 2013, 5, 2589-2620.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

Cited By

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert