The Tumor Necrosis Factor Ligand and Receptor Families

Tumor necrosis factor (TNF) and lymphotoxin-α were isolated more than 10 years ago, on the basis of their ability to kill tumor cells in vitro and to cause hemorrhagic necrosis of transplantable tumors in mice.1 The complementary DNAs and genes encoding each protein were cloned immediately thereafter.2,3 Concurrently, a factor known as cachectin was isolated from mouse macrophages, sequenced, and shown to be identical to TNF.4,5 Cachectin was identified not as a cytolysin, but as a catabolic hormone that suppressed the expression of lipoprotein lipase and other anabolic enzymes in fat.68 Still other studies demonstrated the powerful . . .