Targeting the lipopolysaccharides: still a matter of debate?

The intention of this article is to review endotoxin, host response to endotoxin, clinical significance of endotoxemia, past failed therapies targeting endotoxin, current therapeutic efforts in this area and the authors' opinion on the future of such therapy.

Endotoxin or lipopolysaccharide is implicated in the activation of cytokine release with the potential to lead to severe sepsis. Therapies targeting endotoxin are very appealing and remain a matter of study and debate. Antiendotoxin antibody studies did not show consistent benefit to warrant its approval for use. Lipid A analog, phospholipid emulsion, and ethyl pyruvate are currently being evaluated for potential clinical use. Polymyxin B as an antiendotoxin strategy has an unacceptable toxicity profile for routine use as an intravenous agent and its use in plasmapheris is too cumbersome. Curcumin and lipopolysaccharide binding peptides, although having a potentially desirable effect on ameliorating endotoxin toxicity, remain to be shown effective in clinical trials. The development of a vaccine against endotoxin carries promise.

The benefits of therapies targeting endotoxin remain to be elucidated. Clinical trials targeting populations with documented endotoxemia are more likely to provide an adequate test of this therapeutic approach. Prophylaxis of high-risk populations should also be considered.