Deadly Sepsis Mechanism Identified

Disruption of necroptosis pathway improves survival in septic mice

(RxWiki News) When patients, often those who are hospitalized in grave condition, develop sepsis, the potentially deadly bloodstream infection causes massive cell death. Now scientists have pinpointed how that happens.

A specific cell pathway called necroptosis appears to protect from lethal inflammation associated with the bloodstream infection.

"Carefully wash hands when visiting hospitalized patients to help prevent sepsis."

Systemic inflammatory response syndrome, usually caused by an infection or trauma, and sepsis are believed to be caused by the cytokine tumor necrosis factor (TNF), though the specific mechanisms are not well understood.

Dr. Peter Vandenabeele, a senior study author from Ghent University and Flanders Institute for Biotechnology in Belgium, explained that engaging TNF receptor 1 activates two opposite pathways: one focused on survival and inflammation, and the other prompts cell death. A switch decides which pathway cells will take.

Researchers used mice to disrupt the two cell pathways. They found that inhibiting or genetically deleting RIPK molecules, which are required for necroptosis, provided complete protection against the deadly systemic inflammatory response syndrome.

Disrupting the other pathway had no impact on lethal systemic inflammatory response syndrome. The findings also were confirmed in a mouse model, where scientists confirmed that RIPK deficiency offered protection.

The finding could be key to treating deadly systemic inflammatory response syndrome and sepsis, giving researchers the opportunity to uncover potential therapeutic targets that could be used to develop novel new drugs.

"Selectively targeting the necroptosis process may be more advantageous than globally blocking TNF because it leaves space for the important anti-infectious functions of TNF," noted Dr. Vandenabeele.

The research was published in journal Immunity.

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Review Date: 
December 29, 2011