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SNUH Researchers step closer to raising sepsis survival rate dramatically

Hit : 1,096 Date : 2019-08-23

Korean researchers have uncovered the cause of toxic substances in sepsis for the first time in the world, taking a step closer to developing a treatment to raise the survival rate of patients with sepsis dramatically.

The research team, led by Professor Kim Hyo-soo at the Seoul National University Hospital’s Research-Driven Hospital Project Inflammation/Metabolism Unit, said it discovered that neutrophils, a type of white blood cell, release harmful cytokines in bacterial infection to kill the germs, damaging the human body. The researchers found a mechanism to control the process, providing a new method to develop a sepsis treatment.

Sepsis is a disease that infects the body with bacterial infections and damages major organs. Around 30 million people develop sepsis a year, and 30 percent of sepsis patients die within a month. Pharmaceutical firms have developed numerous treatments, but the uncertain cause of sepsis and complex disease progressions have made it difficult to achieve meaningful results.

Neutrophils kill bacteria but an excessive release of cytokines, which quickly remove bacteria and damage the body, should be avoided. Thus, it is difficult to find the right balance. Despite the eradication of bacteria, the patient could still die, which was the stumbling block in sepsis treatment.

The leading cause of sepsis is endotoxin, a toxin in bacteria. The researchers investigated why endotoxins release large amounts of cytokines from leukocytes and damage the body.

The researchers found that “MYD88 (myeloid differentiation primary response protein) palmitoylation” induced by bacterial endotoxins was important. MYD88 is an inflammation-mediated protein in white blood cells. Palmitoylation is a process in which a lipid is bound to a protein, and the activity of the protein is modified.

The research team administered fatty acid synthase (FASN) inhibitor, which produces palmitic acid, a material for palmitoylation, to mice with sepsis. The result showed that mice treated with FASN inhibitor significantly improved survival rate with fewer abdominal infections.

“We found the mechanism in sepsis where white blood cells cause a cytokine storm that harms the human body, and we are the first to identify key enzymes that can control this properly,” Kim said. “If we develop a substance that can selectively control key enzymes, we will be able to develop a treatment to improve patient survival by making white blood cells selectively kill bacteria without damaging other parts of the body.”

The study was published in the online issue of Nature Chemical Biology on Aug. 19.

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