The search for the cause of hemorrhagic necrosis in tumors led to the discovery of tumor necrosis factor (TNF). This cytokine is a protein that exists in both soluble (157 amino acids long) and transmembrane form (233 amino acids long), produced primarily by macrophages in response to various inflammatory stimuli. It mediates its action through two distinct receptors, a p60 form and a p80 form. Extensive research within the last 15 years has revealed that although TNF is required for protection against bacterial infection, it is involved in cell growth modulation, viral replication, immune system regulation. septic shock, autoimmune diseases, rheumatoid arthritis, inflammation, and diabetes. Agents that can block TNF action, such as thalidomide, soluble TNF receptors, and anti-TNF antibodies, have been approved for human use for autoimmunodeficiency disease syndrome (AIDS), rheumatoid arthritis, and inflammatory bowel disease, respectively.

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