Toll-free road from sepsis

Immune system failure to limit the spread of a bacterial infection results in sepsis: a loss of control on the normal inflammatory response, leading to tissue damage, increased vascular permeability, and finally multi-organ failure and shock. The death rate for sepsis patients is in the range of 70%, and the health-care sticker price for such runaway infections is around $15 billion annually in the US alone. Strategies for treating septic shock are aimed at limiting the inflammatory response, as treatments to directly reduce the bacterial infection, such as the use of antibiotics, can result in furthering the already out-of-control inflammatory response. Now, Cartson Kirschning and colleagues, from the Technical University of Munich, have tested a new therapeutic possibility by creating antibodies directed against the receptor to which bacteria bind in order to infect the cell. The strategy here, therefore, is to interrupt the initial step of septic inflammation. They showed that use of antibodies against the toll-like receptor 2 (TLR2) in lipopeptide-challenged mice blocked the release of markers of the inflammatory response, such as TNFalpha, and protected the mice from a lethal shock-like syndrome. The results here indicate the potential suitability for antibody-directed therapy in treating septic shock.

An accompanying commentary by Thomas Decker, of the University of Vienna, provides an overview of Toll-like receptors, their role in bacterial infection, and a discussion of the potential strengths and weaknesses of targeting these receptors for combating sepsis.

TITLE: Antagonistic antibody prevents toll-like receptor 2–driven lethal shock-like syndromes

AUTHOR CONTACT:
Carsten J. Kirschning
Technical University of Munich, Munich, Germany.
Phone: +49-89-4140-4132; Fax: +49-89-4140-4139; E-mail: carsten.kirschning@lrz.tum.de

View the PDF of this article at: http://www.jci.org/cgi/content/full/113/10/1473

ACCOMPANYING COMMENTARY: Sepsis: avoiding its deadly toll

AUTHOR CONTACT:
Thomas Decker
University of Vienna, Vienna, Austria.
Phone: +43-1-4277-54605; Fax: +43-1-4277-9546; E-mail: thomas.decker@univie.ac.at

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