Tumour Necrosis Factor and Related Cytotoxins

The number of factors implicated in the regulation of cell proliferation is considerable. This book concentrates on tumour necrosis factor (cachectin) and lymhotoxin but includes observations of their interactions with other cytokines, especially the interferons and interleukins.

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The number of factors implicated in the regulation of cell proliferation and differentiation is already considerable and more are continually being identified. This book concentrates on tumour necrosis factor (cachectin) and lymphotoxin but includes observations of their interactions with other cytokines, especially the interferons and interleukins. Molecular studies described here reveal that TNF and lymphotoxin have strong structural homology and act via a common receptor but differ in some of their functional properties. TNF can be either cytostatic or cytotoxic to cultured cell lines, and a variety of mechanisms are proposed, ranging from DNA fragmentation to activation of phospholipases. TNF is also reported to stimulate the growth of normal fibroblasts in vitro. The basis of cell sensitivity or resistance to TNF is unknown and several possibilities are discussed. The in vitro actions of TNF described here include haemorrhagic necrosis of tumours, cachexia, effects on the vasculature, and antiparasitic and antiviral activities.
TNF is shown to be produced not only in macrophages but also in natural killer cells and mast cells, suggesting that it could be a potent regulator of inflammatory and immunological responses. The 'true' function of TNF in either an individual or a species is the subject for some lively debate but remains undetermined. Finally, some interesting data are presented from the first stages of clinical trials of TNF as an anticancer agent.