Public Release: 

Host response to anthrax lethal toxin suggests some current treatment strategies are inappropriate

JCI Journals

Anthrax, a disease previously primarily relevant to the livestock-management community recently became a wordwide bioterrorism concern. However, human anthrax infection is primarily a result of direct or indirect contact with infected animals or exposure to contaminated animal products.

Bacillus anthracis, the causative agent of anthrax, is believed to induce disease and death in humans in an endotoxic shock-like manner. A comprehensive study of the effects of anthrax lethal toxin in mice by Stephen Leppla and colleagues at the National Institutes of Health demonstrated that toxin-induced death does not result from septic shock mediated by cytokine release as previously thought, but via hypoxia-induced liver failure. The study strongly suggests that the therapies developed for the treatment of cytokine-mediated septic shock will not be appropriate for the treatment of anthrax.

In an accompanying commentary, Alice Prince from Columbia University College of Physicians and Surgeons in New York states that "this analysis of the pathological effects of the B. anthracis lethal toxin should help focus future studies of optimal therapy for patients exposed to this organism. These results make clear that anthrax patients exhibit a unique pathophysiology and should not be considered to have generic shock analogous to Gram-negative sepsis". Prince continues "exactly how the lethal factor produces such profound tissue hypoxia, what metabolic processes are affected in the liver and elsewhere, and how these effects may be blocked will require further studies".

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TITLE: Bacillus anthracis lethal toxin induces TNF-alpha-independent hypoxia-mediated toxicity in mice

AUTHOR CONTACT:
Stephen Leppla
National Institutes of Health, Bethesda, Maryland, USA
Phone: 301-594-2865
Fax: 301-480-0326
E-mail: Leppla@nih.gov
View the PDF of this article at: http://www.jci.org/cgi/content/full/112/5/670.

ACCOMPANYING COMMENTARY:
The host response to anthrax lethal toxin: unexpected observations

AUTHOR CONTACT:
Alice S. Prince
Columbia University College of Physicians and Surgeons, New York, New York, USA
Phone: 212-305-4193
Fax: 212-305-2284
E-mail: asp7@columbia.edu

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