Interleukin 1, tumour necrosis factor-alpha (cachectin) and the pathogenesis of cancer cachexia.

Soluble proteins synthesized and released by phagocytic cells may be responsible for the protein and energy wasting frequently observed during catabolic states, including cancer cachexia. This hypothesis is based upon the observation that many of the hosts's metabolic responses to infection, inflammation, accidental trauma and some forms of cancer are remarkably similar. Anorexia and degradation of skeletal and connective tissue protein, as well as increases in hepatic protein synthesis and energy expenditure, can all be reproduced by the administration of activated macrophage products. During inflammatory states, including active tumour growth, increased production of some cytokines, including interleukin 1 and tumour necrosis factor-alpha (cachectin), have been observed. If these monokines serve as metabolic inducers, then efforts to block therapeutically the actions of macrophage-secreted substances may play a role in slowing the progression of tissue-wasting associated with catabolic states, particularly due to malignant tumours.