fig1

Figure 1. The origin and propagation (vicious cycle) of hyperinflammation. In case of hyperinflammation, inappropriate (increased) levels of pro-inflammatory cytokines or (decreased) levels of anti-inflammatory cytokines (M1/M2 paradigm) initiate a vicious circle as non-phagocytized apoptotic vesicles become necrotic and continue the activation of resting macrophages/microglia into M1 macrophages/microglia. Thus, ongoing signaling pathways prolong the cytokine cascade with activation of other immune cell types which promote cell proliferation, boost the pro-inflammatory cytokine release (mainly IL-6), and thus promotes the propagation of tissue damage. In the figure, the blood-brain-barrier (BBB) is shown with the systemic compartment (blood) on the left and the CNS compartment at the right side. In case of hyperinflammation, BBB permeability is increased.