Toll-like receptor-4 antagonist eritoran tetrasodium for severe sepsis

Abstract

The human innate immune system initiates inflammation in response to bacterial molecules, particularly Gram-negative bacterial endotoxin. The steps by which endotoxin exposure leads to systemic inflammation include binding to Toll-like receptor-4 that specifically recognizes endotoxin and subsequently triggers cellular and molecular inflammatory responses. Severe sepsis is a systemic inflammatory response to infection that induces organ dysfunction and threatens a person’s survival. Severe sepsis is frequently associated with increased blood levels of endotoxin. It is a significant medical problem that effects approximately 700,000 patients every year in the USA, resulting in 250,000 deaths. Eritoran tetrasodium is a nonpathogenic analog of bacterial endotoxin that antagonizes inflammatory signaling by the immune receptor Toll-like receptor-4. Eritoran is being evaluated for the treatment of patients with severe sepsis.

Keywords::

• E5564
• endotoxin
• eritoran tetrasodium
• sepsis
• severe sepsis
• TLR-4

Financial & competing interests disclosure

Mark Tidswell serves on the International Executive Advisory Board for the Phase III International Trial of Eritoran, Eisai Medical Research. He receives investigator support from Eisai Medical Research, Ferring Pharmaceuticals A/S and Spectral Diagnostics, Inc. He has received consulting fees from Pfizer Inc. and Eisai Medical Research. Steven P LaRosa receives investigator grants for his role as Director of the Ocean State Clinical Coordinating Center for studies done by Eisai Medical Research (eritoran), AstraZeneca (CytoFab), and Agennix AG (talactoferrin). He receives consulting fees from Artisan Pharma (recombinant soluble thrombomodulin) and Eisai Medical Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.