06:31pm Wednesday 20 September 2017

Targeted blocking of necroptosis prevents fatal condition septic shock

“This research opens up new perspectives for the treatment of fatal inflammatory diseases such as sepsis,” says researcher Peter Vandenabeele of VIB and UGent. “By blocking necroptosis, we have found a possibly new target for a therapy.”

Sepsis and SIRS

The Ghent scientists studied the Systemic Inflammatory Response Syndrome (SIRS). This is a severe inflammatory reaction affecting the entire body. It may be caused by an infection, such as sepsis, or by physical injury such as severe burns or a serious road accident.

Role of TNF in SIRS

The cytokine tumor necrosis factor (TNF) plays a crucial role in the occurrence of SIRS. The presence of TNF may trigger the cells to cause inflammation and programmed cell death. Inflammation is a necessary response in the body generated, among other things, to prevent or restore damage when injury and infections have been sustained. Programmed cell death can occur in two ways: via apoptosis or via necroptosis. The difference between the two forms of cell death lies among other things in communication with our immune system. Necroptosis usually provokes a strong reaction by the immune system whereas apoptosis proceeds unnoticed.

RIPK: potential therapeutic target for treatment of SIRS and sepsis

Peter Vandenabeele and his colleagues Linde Duprez, Nozomi Takahashi and Anje Cauwels have discovered that in mice eliminating apoptosis did not have any impact on lethal SIRS whereas eliminating nepcroptosis afforded full protection against the condition. The scientists managed to block nepcroptosis by eliminating RIPK (Receptor-interacting serine/threonine-protein kinase) molecules. The experiments showed that RIPK plays a crucial role in SIRS and sepsis. The molecule appears to constitute a potential therapeutic target for the treatment of SIRS and sepsis. Further research should clarify the potential applications of this discovery.

Relevant publication
Linde Duprez et al, RIP Kinase-Dependent Necrosis Drives Lethal Systemic Inflammatory Response Syndrome, Immunity, 2011.

Funding
The research was funded by FWO Vlaanderen, IWT, the European Community, the Belgian federal government , UGent, VIB and the Flemish government (Methusalem).


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