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Sepsis risk increased due to the absence of one key enzyme

The presence of caspase-12, touted as the wonder enzyme in sepsis increases the bodys vulnerability to bacterial infection and septic shock while a deficiency confers strong resistance to sepsis. //

This enzyme appears to modulate inflammation and innate immunity in humans.

"The results of the study make clear that caspase-12 plays a critical role in the elimination of bacterial pathogens, and that a deficiency allows systemic and abdominal infections to be better resolved. It's known that the presence of caspase-12 as a full length protein occurs in a small percentage of people of African descent. As a result, some of these individuals are far more susceptible to severe sepsis and have a significantly increased risk of dying from it," said Richard Ulevitch, chair of the Scripps Research Immunology Department and an author of the paper. The study appears in Nature.

The new study showed that caspase-12 deficient mice were resistant to peritonitis and septic shock and were able to clear pathogenic bacteria more efficiently than mice with the enzyme.

Ulevitch said, "Without the experimental model of peritonitis perfected by John Mathison from Scripps Research, we would not have been able to differentiate between the two mouse phenotypes. Because of his work, we were able to use a surgically implanted stent in the colon that allowed a gradual occurrence of sepsis and easy identification. The resulting beneficial effect of cytokine hyper-production runs contrary to some of the current thinking in sepsis research. The general thinking is that this initial cytokine 'storm' is harmful, and that belief has been the basis of a number of unsuccessful clinical studies. In our study, cells containing caspase-12 appear to weaken the activity of caspase-1 that is normally essential for bacterial clearance and sepsis survival."

While caspase-12 was previously thought to be a key mediator of endoplasmic reticulum apoptosis, the new st
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