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Invited review: Mechanisms of endotoxin neutralization by synthetic cationic compounds

Forschungszentrum Borstel, Biophysics Division, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany

Thomas Gutsmann

Forschungszentrum Borstel, Biophysics Division, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany

Patrick Garidel

Institut für Physikalische Chemie, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany

Klaus Brandenburg

Forschungszentrum Borstel, Biophysics Division, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany, Kbranden{at}fz-borstel.de

A basic challenge in the treatment of septic patients in critical care units is the release of bacterial pathogenicity factors such as lipopolysaccharide (LPS, endotoxin) from the cell envelope of Gram-negative bacteria due to killing by antibiotics. LPS aggregates may interact with serum and membrane proteins such as LBP (lipopolysaccharide-binding protein) and CD14 leading to the observed strong reaction of the immune system. Thus, an effective treatment of patients infected by Gram-negative bacteria must comprise beside bacterial killing the neutralization of endotoxins. Here, data are summarized for synthetic compounds indicating the stepwise development to very effective LPS-neutralizing agents. These data include synthetic peptides, based on the endotoxin-binding domains of natural binding proteins such as lactoferrin, Limulus anti-LPS factor, NK-lysin, and cathelicidins or based on LPS sequestering polyamines. Many of these compounds could be shown to act not only in vitro, but also in vivo (e.g . in animal models of sepsis), and might be useful in future clinical trials and in sepsis therapy.

Key Words: Septicemia • lipopolysaccharide • endotoxin neutralization

Journal of Endotoxin Research, Vol. 12, No. 5, 261-277 (2006)
DOI: 10.1177/09680519060120050201


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