TNF: its potential as an antitumour agent

Tumour Necrosis Factor (TNF) was discovered on the basis of its capability to induce necrosis of certain tumours in vivo. A brief overview is given of the pleiotropic effects of TNF on a variety of cells, either transformed cells or normal, diploid cells. Many transformed cells are killed by TNF, especially in the presence of interferon-gamma or inhibitors of transcription or translation. Various activities of TNF on normal cells have been studied, especially those on the endothelial system; these effects may be relevant to an understanding of its toxicity. TNF presumably acts by activation of phospholipase-A2. A number of genes are induced by TNF and, for example, many cells produce interleukin-6. The latter acts on B-cells, on T-cells, on bone marrow cells and, last but not least, on hepatocytes, which results in the synthesis of acute phase proteins. Although the toxicity of TNF, especially in the presence of interferon, limits its wide applicability, it can nevertheless lead to complete tumour curing in experimental animals. Reduction of its toxicity, e.g. by indomethacin treatment, opens new possibilities for TNF as an antitumour drug, alone or in combination with interferon.