Antiendotoxin

Antiendotoxin refers to substances or strategies that counteract endotoxins, primarily lipopolysaccharide (LPS) from the outer membrane of Gram-negative bacteria. Endotoxins can enter the bloodstream during severe infection and contribute to systemic inflammation, septic shock, and organ dysfunction. Antiendotoxin approaches aim to neutralize, remove, or blunt the host response to endotoxin.

Mechanisms of action include direct neutralization by antibodies or LPS-binding proteins that block LPS from engaging cellular receptors, sequestration or physical removal by devices or adsorbents that bind LPS, and inhibition of downstream signaling pathways such as Toll-like receptor 4 (TLR4)–mediated effects. Some strategies also seek to remove circulating endotoxin through extracorporeal therapies.

Clinical approaches and examples have included antiendotoxin antibodies, such as monoclonal antibodies against LPS, and TLR4 antagonists that aim to dampen the inflammatory cascade. Polymyxin B–based therapies can bind and neutralize LPS, and devices containing polymyxin B or other LPS adsorbents have been used in select settings to reduce endotoxin levels. Despite initial promise, many antiendotoxin therapies have not demonstrated consistent, meaningful improvements in mortality in large randomized trials, and none has become standard of care for sepsis. Some applications, such as endotoxin adsorption devices, remain used in limited or region-specific contexts with mixed evidence.

Research continues into targeted endotoxin neutralization and host-response modulation, with emphasis on identifying subgroups that may benefit and on combining antiendotoxin strategies with standard sepsis care.