Lipopolysaccharide (Endotoxin) (LPS)

Lipopolysaccharide (LPS), commonly referred to as endotoxin, is a major glycolipid component of the outer membrane of Gram-negative bacteria and serves as the primary molecular driver of endotoxemia (NIH, 2024; StatPearls, 2024). It consists of three structural domains: a variable O-antigen, a core oligosaccharide, and a highly conserved Lipid A moiety, the latter of which is responsible for its potent toxic effects (PubMed, 2021). Upon entering the systemic circulation, LPS binds to Lipopolysaccharide-Binding Protein (LBP) and is transferred to the CD14/Toll-like receptor 4 (TLR4)/MD-2 complex on immune cells, triggering an intense pro-inflammatory response (PubMed, 2022). This interaction stimulates the release of cytokines such as TNF-alpha and IL-6, which can lead to systemic inflammatory response syndrome (SIRS), sepsis, and lethal septic shock (UniProt, 2023). Therapeutic strategies aimed at managing endotoxemia include direct neutralization of the Lipid A moiety using cationic peptides like Polymyxin B, competitive antagonism of the TLR4 receptor complex with synthetic analogs such as Eritoran, or physical removal of circulating LPS through extracorporeal hemoperfusion (PubMed, 2024; Wikipedia, 2025).

Other names

EndotoxinBacterial lipopolysaccharidesLipid AO-antigenPyrogen

Direct binding and neutralization of the Lipid A moiety; antagonism of the TLR4/MD-2 receptor complex; extracorporeal adsorption and removal from blood; enzymatic detoxification by dephosphorylation.