Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for
sepsis treatment, as
antibiotics are not sufficient to improve outcome during
septic shock. An extracorporeal removal method by
polymyxin (PMX) B direct
hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP
therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by
lipoproteins, including LDLs.
Lipoproteins are critical for physiological LPS clearance, as LPSs are carried by LDLs to the liver for elimination. We hypothesized that
LDL apheresis could be an alternate method for LPS removal. First, we demonstrated in vitro that
LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in PBS. We found that PMX was also adsorbing
lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by
LDL apheresis for
familial hypercholesterolemia is also removed during their
LDL apheresis sessions, with both electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of
septic shock and
severe sepsis patients with gram-negative
bacteremia was also removed in vitro by
LDL adsorption. Overall, these results underline the importance of
lipoproteins for LPS clearance, making them a prime target to study and treat
endotoxemia-related conditions.