New cachexic factors.

Abstract

Patients with pancreatic cancer show evidence of cachexia at the time of diagnosis, involving not only loss of adipose tissue, but also lean body mass. The shorter survival time of men than women with non-small cell lung cancer has been attributed to their enhanced rate of weight loss. From studies in animal models, various cytokines have been proposed as mediators of the cachectic process, although evidence from human studies is generally lacking. Only serum levels of IL-6 have been found to correlate with the clinical development of cachexia, but this may be a marker for the process rather than the actual mediator, because the direct administration of this cytokine to experimental animals failed to induce cachexia, despite the induction of an acute-phase response. Ciliary neurotrophic factor, a member of the IL-6 superfamily, has, however, been shown to produce loss of muscle mass in experimental animals, although it failed to exert a direct catabolic effect on muscle in vitro. A sulphated glycoprotein found in the urine of patients with cancer cachexia is capable of directly inducing protein catabolism in skeletal muscle by a process involving an increase in prostaglandin E2. Agents capable of attenuating this effect, e.g. eicosapentaenoic acid and ibuprofen, have been shown to stabilize body weight loss in cachectic cancer patients. This pharmacological approach to the treatment of cachexia appears to be more successful than nutritional manipulation.