ABSTRACT

This chapter discusses tumor necrosis factor/cachectin as tumor necrosis factor (TNF) for the sake of brevity, although both names are appropriate. Numerous discoveries revolutionized tumor necrosis factor/cachectin research in 1985. The originators described two distinct properties in the hypersensitive shock sera: the capacity to passively induce the necrosis of solid intradermal tumor implants in vivo, and toxicity to cultured tumor cell lines. Intradermal tumor necrosis is perhaps the most dramatic and vivid property of TNF. Mice bearing solid tumor implants are injected i.v. with test material. The intradermal tumor may represent a specialized case of effectiveness. Tumor-bearing mice are more sensitive to endotoxin. Cell death requires hours to days of exposure. Toxicity surveys of established cell lines concluded that many tumor lines were sensitive, that the species of origin was irrelevant, and that normal cells were insensitive. TNF, lymphotoxin, and gamma interferon have been shown to increase the phagocytic and antibody-dependent cellular cytotoxic capacities of human neutrophils.