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Mouse study gives new view of anthrax toxin

A large-scale study of anthrax in mice has yielded new information about immune system response to anthrax bacteria, according to scientists at the National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health. The discovery that toxins released by the bacteria do not behave as previously believed should redirect approaches to anthrax drug design, notes NIAID Senior Investigator Stephen Leppla, Ph.D., whose research is published in today's issue of the Journal of Clinical Investigation.

In the new study, Dr. Leppla and his colleagues injected hundreds of inbred mice with anthrax lethal toxin (LT), and then took precisely timed measurements to determine how various organs and immune system processes responded. For example, they measured levels of chemicals called cytokines, which are released by immune system cells after a bacterial invasion. Dr. Leppla and his colleagues found no evidence of a persistent increase in cytokines, or of a link between cytokine increase and anthrax LT effects, contradicting earlier beliefs.

The evidence suggests that current efforts to design cytokine-suppressing drugs to treat lethal toxin-mediated events in late stages of anthrax may be misguided. "Finding effective therapies for diseases such as inhalational anthrax depends on our ability to connect basic research with clinicians' needs. This research is a perfect example of such translational research," says NIAID Director Anthony S. Fauci, M.D.

"Science has had a good understanding of anthrax toxins at molecular and subcellular levels," says Dr. Leppla. "What has been lacking is a picture of the much more complex effects of toxins on tissues and animal models. Ours is one of the first comprehensive studies to critically examine what is actually happening at these higher levels of complexity."

In a natural infection, inhalational anthrax begins after anthrax bacteria spores enter the body, germinate and rel
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Contact: Anne A. Oplinger
aoplinger@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
2-Sep-2003


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