Cytokines and cancer anorexia cachexia syndrome. Am J Hosp Palliat Care. 2008; 25(5):407–11. Epub 2008/04/12. doi: 1049909108315518 [pii] doi: 10.1177/ 1049909108315518 PMID

Anorexia, defined as the loss of desire to eat in the face of caloric deprivation, is a prevalent symptom in advanced cancer.5 Anorexia alone does not explain the magnitude of weight loss seen in cancer: cachexia can be pres-ent in the absence of anorexia. Furthermore, nutri-tional support does not restore LBM in CACS.6 Cancer anorexia is the consequence of altered cen-tral and peripheral neurohormonal signals that con-trol appetite. Proinflammatory cytokines such as tumor-necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, and interferon-γ (IFN-γ) are fundamental to the patho-physiology of CACS. These cytokines overlap in activity and produce many of the features seen in CACS.7 However, the mechanisms by which proin-flammatory cytokines evolve CACS are not well defined. IL-1 influences size, duration, and frequency of meals in rats through signaling in the hypothala-mus.8 Inhibition of IL-1 expression or antibodies to IL-1 improve appetite and weight gain in tumor-bearing (TB) animals.9 Cytokines, especially IL-1, increase in the hypothalamus and enhance sero-toninergic tone through tryptophan, which increases in the hypothalamus.10 As a consequence, pro-opiomelanocortin neurons are activated in TB animals, which is thought to be responsible for anorexia