ABSTRACT
The initial bioassay for Tumor Necrosis Factor (TNF) -α involved hemorrhagic necrosis, in vivo, of a methyl- cholanthrene transformed sarcoma in mice. Due to the limited supply of TNF-α and -ß available from natural sources, it was extremely important that the genes for both the proteins be isolated, cloned, and expressed in order to make large quantities of the protein available. One of the major biological effects of TNFs, as their names imply, is the in vivo destruction of certain tumors. In contrast to cytotoxic activity of TNF-α and TNF-ß for a number of tumor cells, they both directly stimulate the growth of normal fibroblasts. Tumor necrosis serum and partially purified preparations of TNF-α have been reported to protect animals against bacterial and parasitic infections. Several laboratories have used radiolabeled TNFs to demonstrate that TNFs bind to specific cell surface receptors. Mechanistic studies have been most extensively carried out on the in vitro cytotoxicity of TNF to L-929 cells.
