Significance of endotoxin removal therapy; from a basic point of view

Abstract

Until recently, endotoxin (lipopolysaccharides-LPS) shock was not suspected to be caused primarily by the recognition of LPS by cell surface Toll-like receptor (TLR) -4. However, in 2013, intracellular caspase was discovered as a TLR-4-independent LPS sensor. Endotoxin shock can be defined as intracellular caspase-mediated pyroptosis (cell death), caused by intracellular LPS. Recent studies suggested an underlying pulmonary injury mechanism in endotoxin shock, where LPS in the blood is directly transported to the pulmonary vascular endothelial cells, to cause pyroptosis. These studies might imply the significance of removing LPS from the blood. However, even in the EUPHRATES study on polymyxin B direct hemoperfusion (PMX-DHP), the method of direct quantification of LPS was not adopted, and thus, the effect of removing LPS remains unknown. Hence, the outcome of endotoxin adsorption therapy, conducted in patients with high LPS levels, using optimal procedures with appropriate primary endpoints, should be evaluated.