The role of cytokines in cancer cachexia

A large number of observations point towards cytokines, polypeptides releas ed mainly by immune cells, as the molecules responsible for the metabolic d erangements associated with cancer-bearing states. Indeed, these alteration s lead to a pathological state known as cancer cachexia which is, unfortuna tely, one of the worst effects of malignancy, accounting for nearly a third of cancer deaths. It is characterized by weight loss together with anorexi a, weakness, anemia, and asthenia. The complications associated with the ap pearance of the cachectic syndrome affect both the physiological and bioche mical balance of the patient and have effects on the efficiency of the anti cancer treatment, resulting in a considerably decreased survival time. At t he metabolic level, cachexia is associated with loss of skeletal muscle pro tein together with a depletion of body lipid stores. The cachectic patient, in addition to having practically no adipose tissue, is basically subject to an important muscle wastage manifested as an excessive nitrogen loss, Th e metabolic changes are partially mediated by alterations in circulating ho rmone concentrations (insulin, glucagon, and glucocorticoids in particular) or in their effectiveness. The present study reviews the involvement of di fferent cytokines in the metabolic and physiological alterations associated with tumor burden and cachexia, Among these cytokines, some can be conside red as procachectic (such as tumor necrosis factor-alpha), while others hav ing opposite effects can be named as anticachectic cytokines. It is the bal ance between these two cytokine types that finally seems to have a key role in cancer cachexia. (C) John Wiley & Sons, Inc.