[The possible modes of action of TNF (tumor necrosis factor)]

TNF has been characterized by the fact that it not only induces hemorrhagic necrosis in various established tumors including Meth. A in vivo but also shows antitumor activity against several transformed cell lines in vitro. However, most studies on TNF have been carried out not with purified Preparations but with mouse or rabbit serum containing other cytokines like INF or with so-called tumor necrosis serum (TNS). Therefore, it is somewhat difficult and rather early to review the action mechanisms of TNF. According to a few reports which have used TNS to study the node of he action of TNF in vitro, its activity against transformed cell lines can be tentatively summarized as follows. First, the TNF molecule binds to the corresponding receptor on the cell surface, and then is transferred to the lysosome in a similar manner to the internalization of growth hormone and insulin. The TNF on the lysosomal membrane their induces injury to the membrane as a labilizer, finally causing cell destruction. TNF seems to be a cytotoxic rather than cytolytic substance. However, this recently described mechanism in vitro is not able to explain how TNF causes the central hemorrhagic necrosis of established solid tumors in vivo. Many unknown action mechanisms of TNF still remain to be clarified.