Background

Tumor necrosis factor-alpha (TNFα) in humans is a pleiotropic inflammatory cytokine. It is expressed by many different stimulated cell types including monocytes, endothelial cells, fibroblasts and both T and B-lymphocytes, but especially by macrophages. It affects most organs. The production of TNF alpha is induced by IL-1, PDGF, IFN-beta, NGF, Oncostatin M and certain fungal, viral, and parasitic invasions. Bacterial lipopolysaccharide is an especially potent stimulus. The primary role of TNFα is in the regulation of immune cells. TNF α mediates septic shock in response to infection. It initiates a cascade of cytokines and increases vascular permeability, thereby recruiting macrophages and neutrophils. TNFα secreted by macrophages causes blood clotting which helps contain infection. TNFα is also able to induce apoptotic cell death or inflammation, and to inhibit viral replication. It possesses growth stimulating, inhibitory, and self regulatory properties. Dysregulation of TNFα production has been implicated in a variety of human diseases, as well as cancer. The presence of TNFα is responsible for diverse immunomodulatory and toxic effects. For instance, TNFα induces neutrophil proliferation during inflammation, but it also induces neutrophil apoptosis upon binding to the TNF-R55 receptor. TNFα causes necrosis of some types of tumors, but promotes growth of other types. Low levels may aid in maintaining homeostasis by regulating the body's circadian rhythm, and may promote remodeling or replacement of injured and senescent tissue by stimulating fibroblast growth. High levels of TNFα correlate with increased risk of mortality.