Tumour necrosis factors in clinical practice.

The tumour necrosis factors are pleiotropic proteins which have a wide range of biological activities. Tumour necrosis factor-alpha or cachectin is a product of macrophages and is the principal host mediator of septic shock and the cachexia of chronic disease. A related molecule, tumour necrosis factor-beta or lymphotoxin, is produced by T lymphocytes in response to antigen or mitogens. The role of the TNFs in disease processes and in therapy are reviewed. Both agents exert antiproliferative effects on certain tumour cell lines, while normal cells are resistant to these effects. In vivo, they cause haemorrhagic necrosis of certain implantable tumours in mice. Trials of tumour necrosis factor-alpha as an anticancer agent, either singly or in combination with interferon gamma or cytotoxic drugs, are in progress. Understanding the involvement of the tumour necrosis factors in pathological processes may lead to new therapies for endotoxic shock and cancer.