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New study finds on/off switch for septic shock

NEW YORK, Nov. 14, 2006. According to a new study, septic shock--a dangerous, often deadly runaway immune response--is controlled by a genetic on/off switch. The research also suggests how a drug might temper sepsis. This is the first time this genetic mechanism has been revealed in an experimental animal.

The study by Robert Schneider, Ph.D., the Albert B. Sabin Professor of Microbiology and Molecular Pathogenesis at NYU School of Medicine and his colleagues, is being published in the November 15th print edition of the journal Genes & Development

A killer and a protector

Septic shock is the nation's 10th most frequent cause of death and the leading cause of hospital-related mortality. Bacterial infection, notably the toxins that are part of the bacterial cell wall, stimulate the inflammatory response which can spin out of control. Sepsis progresses swiftly from chills, fever and shallow breathing, to dilated and leaky blood vessels, a lack of blood supply in the body's organs, multiple organ failure and, often, death.

Infection causes the body's immune system to produce protective proteins called cytokines. Problems arise when the body is unable to turn off cytokine production and they overwhelm the body, says Dr. Schneider. "The resulting cytokine storm is, for example, what kills people when they are infected with anthrax and, we think, an important factor in what killed people in the flu pandemic of 1918," he says.

Dr. Schneider and his colleagues focused on one of the key genes that regulate cytokine production called auf1, which has been extensively studied in tissue culture but not in animals. In an attempt to move the research closer to the clinical setting, the team genetically engineered and bred mice lacking the auf1 gene, a so-called knock-out mouse. Then, mice with the gene and mice without it were exposed to a bacterial toxin that causes mild food poisoning. The normal mice had little pro
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Contact: Jennifer Choi
jennifer.choi@nyumc.org
212-404-3555
New York University Medical Center and School of Medicine
14-Nov-2006


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