TLR4 antagonists for endotoxemia and beyond.
Toll-like receptor 4 (TLR4) controls the major responding signaling system that detects the presence of Gram-negative infectious pathogens, by responding to endotoxin from their outer membrane. Normally, TLR-bearing cells signal the immune system to mount a pro-inflammatory, antibacterial response and resolve infection. However, TLR4 can also respond to a variety of 'endogenous' ligands, such as fibronectin and heat shock proteins. Overstimulation or continued stimulation of TLR4 by any ligand can result in a systemic inflammatory response, progressing to hypotension, shock, organ failure and even death. This review discusses current, preclinical and clinical research regarding eritoran (E-5564), an analog of the non-toxic lipid A from Rhodobacter sphaeroides, as well as other antagonists of TLR4 in a variety of diseases.
Rossignol
Daniel P
DP
Eisai Medical Research Inc, NJ 07660, USA. dan_rossignol@eisai.com
Lynn
Melvyn
M
D000818:Animals; D019446:Endotoxemia / Q000188:drug therapy*; D006801:Humans