Fig. 2.

Systemic spread of necroinflammation. Programmed necrosis or defective efferocytosis of dying cells can initiate local inflammation. DAMPs and proinflammatory cytokines derived from necrotic cells and subsequently activated immune cells provide feed-forward signals reinforcing programmed necrosis in more cells. Continuing the vicious death cycle allows the damage of barrier function, the spread of necroinflammation to systemic level, which may ultimately cause devastating multi-organ failure