New Study Finds on/off Switch for Septic Shock -- MEDICA Trade Fair

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. Robert Schneider, Ph.D., the Albert B. Sabin Professor of Microbiology and Molecular Pathogenesis at New York University School of Medicine.

Dr. Schneider and his colleagues focused on one of the key genes that regulate cytokine production called auf1. The researchers genetically engineered and bred mice lacking the auf1 gene. 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 problem fending off the endotoxin. "The mice without the gene died due to an uncontrolled septic-shock like response - their blood vessels burst, their spleens were destroyed," says Dr. Schneider. Mortality was five-fold higher in mice without the auf1 gene.

Further research showed where auf1 functions at the molecular level, he says. In normal mice, the scientists found that auf1 steps into action once the immune response is activated and after cytokine production gets underway. The action is pronounced: messenger RNAs (mRNAs) which are blueprints for very specific cytokines - namely interleukin-1 beta, tumour necrosis factor alpha and COX-2 - are degraded. That process of degrading the mRNAs shuts off production of these cytokines.

In the study, mice lacking the auf1 gene do not seem to have that off switch; their cytokine levels were greatly elevated. A cytokine storm had caused sepsis in these animals. In summary, auf1 is a protector that can stop an infection from progressing to septic shock, explains Dr. Schneider. It does so by helping with cytokine production and then tempering the production of these proteins. Auf1 acts like a cytokine on/off switch.; Source: New York University Medical Center and School of Medicine