Endotoxin elimination in sepsis: physiology and therapeutic application.
OBJECTIVE
The present review summarizes key papers on the elimination of endotoxin in human.


RESULTS
Lipopolysaccharides (LPS) are extremely strong stimulators of inflammatory reactions, act at very low concentrations, and are involved in the pathogenesis of sepsis and septic shock. Elimination of LPS is vital; therefore, therapeutic detoxification of LPS may offer new perspectives. Multiple mechanisms eliminate LPS in human comprising molecules that bind LPS and prevent it from signaling, enzymes that degrade and detoxify LPS, processes that inactivate LPS following uptake into the reticulo-endothelial system, and mechanisms of adaptation that modify target cells responding to LPS. These mechanisms are powerful and detoxification capacity adapts as required. Results of therapeutic interventions aiming at the removal of LPS by medication (immunoglobulins) or extracorporeal means are controversial. At least in part, animal experiments revealed increased survival. Human trials confirmed the positive effects on parameters of secondary importance, but not on morbidity or survival which was attributed to the heterogeneity of patients suffering from consequences of severe infectious diseases and sepsis.


CONCLUSIONS
The hypothesis of LPS-driven inflammatory processes remains very attractive. However, few therapeutic yet immature options have been developed to date.
Buttenschoen
Klaus
K
Department of Surgery, Division of General Surgery, University of Alberta, 8440-112 St, Edmonton, AB, Canada. klaus.buttenschoen@ualberta.ca
Radermacher
Peter
P
Bracht
Hendrik
H
D000818:Animals; D018988:Bacterial Translocation; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000276:immunology* / Q000628:therapy; D004731:Endotoxins / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D011817:Rabbits; D051381:Rats; D018805:Sepsis / Q000276:immunology* / Q000628:therapy; D012772:Shock, Septic / Q000276:immunology / Q000628:therapy; D013552:Swine
D004731:Endotoxins; D008070:Lipopolysaccharides