Perioperative anti-endotoxin strategies

Abstract

Lipopolysaccharides from the outer membrane of Gram-negative bacteria are potent stimuli for the production of numerous cytokines by the immune cells. The systemic inflammatory response to these gut-derived endotoxins is therefore dependent on the responsiveness of the immune system. This paper presents results on anti-endotoxin strategies and the responsiveness to endotoxin in animal models of liver failure. Following partial hepatectomy in the normal rat, anti-endotoxin treatment using the enteral endotoxin binder cholestyramine and the bactericidal permeability-increasing protein showed beneficial effects in terms of reducing the exaggerated metabolic and inflammatory responses. Similar beneficial effects of gut endotoxin restriction were found in bile duct ligated rats subjected to a laparotomy. The beneficial effects of anti-endotoxin strategies in these models were explained by completely different mechanisms. In partial hepatectomized rats the effects were explained by the direct inhibition of the stimulatory action of endotoxin on immune cells preventing an exaggerated inflammatory response. In contrast, in postoperative BDL rats the effects of anti-endotoxin therapy were explained by the restoration of endotoxin sensitivity of the immune cells resulting in an inflammatory response necessary for an adequate reaction to surgery. These different mechanism will be discussed in the light of the phenomenon of endotoxin tolerance.