TNF-alpha is a pro-inflammatory cytokine critical to the innate immune response and is produced by macrophages and monocytes. It increases the permeability of the vascular endothelium, which allows other cells of the immune system (like neutrophils) to travel to the site of infection. Clinical manifestations of this cytokine include prolonged, febrile illnes. TNF-alpha also plays a role in cell apoptosis and necrosis. Additionally, through the induction of a complex cytokine signaling pathway, transcription factors are activated which go on to express inflammatory cytokines. Common treatments for overexpression of TNF-alpha are TNF inhibitors.