An Inflammatory Perspective on Necroptosis

Necroptosis (programmed necrosis) occurs in response to TNF, Fas, or TRAIL, as well as certain TLR ligands, when caspase activity required for apoptosis is blocked. Necroptosis is typically considered a highly pro-inflammatory mode of cell death, due to release of intracellular "danger signals" that promote inflammation. However, because most pro-necroptotic stimuli are intrinsically highly pro-inflammatory-due to their ability to initiate the synthesis of numerous cytokines and chemokines-the inflammatory consequences of necroptosis are complex. Here, we suggest that necroptosis might have anti-inflammatory effects in certain settings, through curbing excessive TNF- or TLR-induced inflammatory cytokine production.