Editing Tumor necrosis factor (section)

== History ==
In the 1890s, [[William Coley]] observed that acute infections could cause tumor regression, leading to his usage of bacterial toxins as a cancer treatment. In 1944, [[endotoxin]] was isolated from Coley's bacterial toxins as the substance responsible for the anticancer effect. In particular, endotoxin could cause tumor regression when injected into mice with experimentally induced cancers. In 1975, Carswell et al. discovered that endotoxin did not directly cause tumor regression, but instead induced [[macrophages]] to secrete a substance that causes tumors to hemorrhage and necrotize, termed "tumor necrosis factor."<ref name="DeathByInflammation"/>

In the 1980s, TNF was purified, sequenced, and cloned in bacteria. Studies on recombinant TNF confirmed the anticancer potential of TNF, but this optimism faded when TNF injections were found to induce endotoxin shock. TNF was also discovered to be the same protein as cachectin, known to cause muscle wasting in mice. These findings demonstrated that TNF could be detrimental in excessive quantities. In 1992, TNF antibodies were found to reduce joint inflammation in mice, revealing TNF's role in inflammatory diseases. This led to the approval of the first [[TNF_inhibitor|anti-TNF]] therapy for [[rheumatoid arthritis]] in 1998.<ref name="DeathByInflammation"/>

=== Nomenclature ===
In 1985, TNF was found to have significant sequential and functional similarity with [[Lymphotoxin_alpha|lymphotoxin]], a previously discovered [[cytokine]]. This led to the renaming of TNF to TNF-α and lymphotoxin to TNF-β. However, in 1993, a protein with close similarity to lymphotoxin was discovered, termed [[Lymphotoxin_beta|lymphotoxin-β]]. In 1998, at the Seventh International TNF Congress, TNF-β was officially renamed to lymphotoxin-α, while TNF-α was renamed back to TNF. Nevertheless, some papers continue to use the term TNF-α.<ref name="TenaciousA">{{cite journal | vauthors = Grimstad Ø | title = Tumor Necrosis Factor and the Tenacious α | journal =  JAMA Dermatology | volume = 152 | issue = 6 | pages = 557 | date = May 2016 | doi = 10.1001/jamadermatol.2015.4322 | pmid = 27168212 | hdl = 10037/10660 | hdl-access = free }}</ref>