Tumour-necrosis factor from the rabbit. III. Relationship to interferons

Tumour-necrosis factor (TNF) is growth-inhibitory or cytotoxic to certain tumour cell lines, and is present in the serum of rabbits injected i.v. with BCG and endotoxin 2 weeks apart (TNF serum). TNF serum also has interferon activity, and as TNF and interferons have a number of properties in common their relationship has been investigated further. TNF was assayed by cytotoxicity in vitro against L cells and interferon by a CPE-inhibition assay with Semliki Forest virus. TNF appears not to be an interferon, on the following bases: 1. TNF activity could be separated from the Type I interferon of TNF serum by passage through a Cibacron blue-agarose column or by sequential salt precipitation, ion-exchange chromatography and gel filtration. 2. Preparations of Type I interferon induced by poly I, poly C or virus lacked TNF activity. 3. Though it was not possible to compare TNF with rabbit Type II interferon (as methods used to induce Type II interferon in other species were unsuccessful in the rabbit) rabbit TNF has a number of properties which distinguish it from the Type II interferons of other species. 4. Rabbit TNF inhibited the growth of a human melanoma cell line, and also had effects on certain mouse and rabbit cell lines, whereas the anti-cellular effects of interferons are reported to be species-specific.