Tumour Necrosis Factor and Related Cytotoxins: (Ciba Foundation Symposium)

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.

Table of Contents:
Natural Production and Release of Tumour Necrosis Factor (G. Gifford, D. Flick). Possible Relationships between in vivo Antitumour Activity and Toxicity of Tumour Necrosis Factor-a (M. Palladino et al.). Human Tumour Necrosis Factors: Structure and Receptor Interactions (B. Aggarwal et al.). Cytocidal Activity of Tumour Necrosis Factor: Protection by Protease Inhibitors (C. Baglioni et al.). Lymphotoxin: Cloning, Regulation, and Mechanism of Killing (N. Ruddle et al.). Physiological Responses to Cachectin (K. Tracey et al.). Structure-function Relationship of Tumour Necrosis Factor and Its Mechanism of Action (W. Fiers et al.). Relationship of Tumour Necrosis Factor and Endotoxin to Macrophage Cytotoxicity, Haemorrhagic Necrosis and Lethal shock (J. Rothstein, H. Schreiber). Antitumour Effects of Necrosis Factor: Cytotoxic or Necrotizing Activity and Its Mechanism (K. Haranaka et al.). Effects of Tumour Necrosis Factor on Human Tumour Xenografts in Nude Mice (F. Balkwill et al.). Effects of Tumour Necrosis Factor and Related Cytokines on Vascular Endothelial Cells (J. Pober). Antiparasitic Effects of Tumour Necrosis Factor in vivo and in vitro (J. Playfair, J. Taverne). Clinical Studies with Tumour Necrosis Factor (D. Spriggs et al.). Summary (L. Old). Index of Contributors. Subject Index.