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Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect
Rural Health Academic Center, Melbourne Medical School, University of Melbourne, Parkville 3010, Australia
Division of Internal Medicine, Ballarat Health Services, Ballarat 3350, Australia
Infection Control Committees, St John of God Hospital and Ballarat Health Services, Ballarat 3353, Australia
Received: 31 October 2013; in revised form: 9 December 2013 / Accepted: 13 December 2013 / Published: 18 December 2013
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
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Cite This Article
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.
Hurley JC. Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect. Toxins. 2013; 5(12):2589-2620.
Hurley, James C. 2013. "Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect." Toxins 5, no. 12: 2589-2620.