IMR Press / FBL / Volume 19 / Issue 6 / DOI: 10.2741/4256

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review
Targeting myeloid differentiation 2 for treatment of sepsis
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1 Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, China
Academic Editor:Fei He
Front. Biosci. (Landmark Ed) 2014, 19(6), 904–915; https://doi.org/10.2741/4256
Published: 1 June 2014
(This article belongs to the Special Issue Deregulation of T cell response in sepsis)
Abstract

Sepsis continues to be a leading cause of intensive care unit (ICU) death. Gram-negative bacteria are among the most important pathogens of sepsis and their LPS content is regarded to be an important stimulator that elicits the systemic inflammatory reaction. MD-2 is a small secreted glycoprotein that can bind to both the hydrophobic portion of LPS and to the extracellular domain of TLR4. The interaction between MD-2 and LPS bridges the two TLR4 molecules and induces the dimerization of LPS-MD2-TLR4, which forms the structural basis for biological functions of TLR4/MD-2 complex. Due to its essential role in mediating the interaction between LPS and TLR4, MD-2 has been extensively explored as a therapeutic target for treatment of inflammatory disorders such as sepsis. Eritoran is a synthetic tetraacylated lipid A that binds directly to MD-2 and antagonizes LPS binding to the same site. Although eritoran showed positive results in phase I and phase II clinical trials of severe sepsis, a phase III clinical study for severe sepsis has failed. More effective therapeutic strategies are in need to treat this devastating clinical disorder.

Keywords
Eritoran
lipopolysaccharide
myeloid differentiation 2
sepsis
Toll like receptor 4
Review
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