The Role of Cytokines in Cancer Cachexia

Abstract

A large number of observations point towards cytokines, polypeptides released mainly by immune cells, as the molecules responsible for the metabolic derangements associated with cancer-bearing states. Indeed, these alterations lead to a pathological state known as cancer cachexia which is, unfortunately, one of the worst effects of malignancy, accounting for nearly a third of cancer deaths. It is characterized by weight loss together with anorexia, weakness, anemia, and asthenia. The complications associated with the appearance of the cachectic syndrome affect both the physiological and biochemical balance of the patient and have effects on the efficiency of the anticancer treatment, resulting in a considerably decreased survival time. At the metabolic level, cachexia is associated with loss of skeletal muscle protein 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. The metabolic changes are partially mediated by alterations in circulating hormone concentrations (insulin, glucagon, and glucocorticoids in particular) or in their effectiveness. The present study reviews the involvement of different cytokines in the metabolic and physiological alterations associated with tumor burden and cachexia. Among these cytokines, some can be considered as procachectic (such as tumor necrosis factor-␣), while others having opposite effects can be named as anticachectic cytokines. It is the balance between these two cytokine types that finally seems to have a key role in cancer cachexia.

Genetic Ablation of TWEAK Augments Regeneration and Post-Injury Growth of Skeletal Muscle in Mice

“…13 Coincidently, these pro-inflammatory cytokines have also been suggested as the major mediators of skeletal muscle-wasting in chronic diseases. 14,15 TNF-like weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine belonging to TNF super family ligands. 16 TWEAK is initially synthesized as a type II transmembrane protein, cleaved to its soluble form, and signals as a trimerized molecule.…”

Role of nutritional intervention in patients treated with radiotherapy for pelvic malignancy

“…Malnutrition per se is an independent adverse prognostic factor in many cancers (Bozzetti, 2001). It may occur due to physiological, metabolic, psychological or iatrogenic processes, which exist as a result of malignancy and may affect morbidity, mortality and response to treatment (Argiles and Lopez-Soriano, 1999).…”

Longitudinal assessment of nutritional risk in patients under chemo or radiotherapy

“…In the last decade, it has been postulated that inflammation plays a central role in the cachexia of cancer, based on studies showing the effects of inflammatory mediators such as TNF-alpha, IFN-gamma, IL-1, IL-6. [19][20][21] In this context, in addition to nutritional counseling with the purpose of reducing the nutritional risk, a major scientific challenge in this area is to develop studies evaluating the effect of specific nutrients to reduce inflammatory cytokines involved in the etiology of neoplastic cachexia.…”