Tumor necrosis factor

Abstract

The active component in serum, which is called the tumor necrosis factor (TNF), has now been partially purified and characterized. TNF is a glycoprotein containing sialic acid and galactosamine with a mol. wt. of approximately 150,000. Present indications, all indirect, are that TNF is a product of macrophages. The evidence for this includes: agents which prime for TNF release caused marked macrophage hyperplasia; selective lysis of splenic macrophages is seen shortly after endotoxin injection into BCG primed mice; and serum containing TNF is rich in enzymes of lysosomal origin (activated macrophages are characteristically rich in such lysosomes). Conditions for TNF release (e.g., time after injection of BCG or C. parvum, dosage and timing of endotoxin) have been well established. TNF is active against a variety of mouse tumors, it occurs in the serum of BCG or C. parvum primed mice injected with endotoxin. Although TNF reproduces endotoxin's action on tumors, it remains to be seen whether TNF is, in fact, the mediator of endotoxin induced tumor hemorrhagic necrosis. The possibility that TNF plays a role in the antitumor activity of BCG, C. parvum and other immunopotentiators also needs consideration. As mouse TNF is selectively inhibitory for certain lines of human cancer cells in vitro, it displays a remarkably broad spectrum of antitumor activity. Eventual assessment in the clinic awaits the finding of a more plentiful source of TNF.