Tumor necrosis factor: is it time to change the name?

Among targets of biological agents, tumor necrosis factor remains in the exclusive group that has retained its historical name or at least one of them. Tumor necrosis factor is usually known by the three-letter abbreviation TNF and somehow has escaped a more bland and nondescript moniker such as IL-something. Endogenous pyrogen is now IL-1, B-cell stimulatory factor-2 is now IL-6, and T-cell growth factor is IL-2. But TNF is still TNF. The other name for TNF, cachectin, seems long gone, although arguably the metabolic actions of TNF are more relevant to the setting of inflammatory and autoimmune disease than a capacity to kill tumors. Although the name TNF has withstood the test of time, it depicts few of its myriad activities and little of its profound impact on the function of the brain, liver, and heart among other organs and tissues. The designation TNF or tumor necrosis factor reflects the original discovery in the 1970s of a cytotoxic substance produced by immune cells stimulated by endotoxin. Since in animal models TNF kills tumors, investigators tried to exploit this action therapeutically in patients with cancer, but the administration of this cytokine made recipients too systemically sick. Though limiting TNF’s development in oncology, these studies revealed the powerful role of TNF in immunity. In addition to killing tumors, TNF can cause the metabolic derangements of cachexia as shown initially in studies on a novel factor produced by macrophages stimulated with bacterial or protozoal products. These studies called this factor cachectin. After studies showed that TNF and cachectin are the same molecule, only one name was possible and TNF became it. With the recognition of TNF’s role in inflammation, studies focused on its potential as a target in the treatment of sepsis. Even though studies pointed to the efficacy of TNF blockade in animal models of sepsis, trials in humans were unsuccessful. Fortunately, these trials provided valuable reagents that led to the striking success of TNF blockade in