TNF-alpha release is mainly triggered by viral infections, endotoxins, lipopolysaccharides or other bacterial components, by tissue injury, DNA-damage and by IL-1, PDGF and TNF-alpha itself. It is primarily expressed in macrophages, but also in monocytes, neutrophils, NK-cells, mast-cells, endothelial cells and activated lymphocytes. TNF-alpha expression in endothelial cells and fibroblasts can be induced by IL-17. The expression of other cytokines, chemokines, reactive oxygen intermediates, nitric oxide and prostaglandins is stimulated by TNF-alpha.
Multiple biological functions of TNF-alpha comprise cellular proliferation and differentiation, tumorigenesis, apoptotic or necrotic cell death (including certain tumor cell lines), immunoregulatory activities, lipid metabolism, coagulation and endothelial function. It promotes local or systemic inflammation (TNF-alpha is a potent pyrogen) and stimulates the acute phase response. Very high expressions of TNF-alpha after infection can lead to septic shock (TNF-alpha is highly cytotoxic.), whereas sustained low levels induce cachexia and inflammation. Dysregulation of TNF-alpha is involved in many diseases.