Targeting endotoxin in the treatment of sepsis

The role of endotoxin in the genesis of sepsis has long been recognized and multiple treatments aimed at neutralizing it have been studied. Endotoxin can be bound by antibodies (whose role as a therapeutic agent is unlikely), binding proteins such as BPI or human lactoferrin (effectiveness debated and promising respectively) and phospholipid emulsion (which has not improved outcomes in a recent study). Alternatively, the action of endotoxin could be blocked by lipid A analogs (initial study showed no overall benefit and another large trial is near completion targeting a subpopulation of that study). Finally, endotoxin can be bound by polymyxin B embedded in hemoperfusion cartridges. The later treatment has been used for more than a decade in Japan. Since both pre-clinical rationale and studies support the targeting of endotoxin to ameliorate the pro-inflammatory and pro-coagulation response of severe sepsis, this therapeutic intervention is being pursued.