ORIGINAL ARTICLE Int J Clin Oncol (2009) 14:315–320 © The Japan Society of Clinical Oncology 2009 DOI 10.1007/s10147-008-0856-1 M. Takahashi · K. Oyama · H. Fujiwara · G. Wakabayashi Department of Surgery, Iwate Medical University, Morioka, Japan M. Terashima (*) Department of Surgery, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan Tel. +81-24-548-2111; Fax +81-24-548-2735 e-mail: mterashi@fmu.ac.jp A. Takagane Department of Surgery, Hakodate Goryokaku Hospital, Hakodate, Japan Masanori Takahashi · Masanori Terashima Akinori Takagane · Kenichi Oyama · Hisataka Fujiwara Go Wakabayashi Ghrelin and leptin levels in cachectic patients with cancer of the digestive organs Key words Cachexia · Cancer of the digestive organs · Cytokine · Ghrelin · Leptin · Body mass index Introduction Cancer cachexia is characterized by progressive emaciation involving depletion of host adipose tissue stores. 1 Patients with this disorder suffer from numerous symptoms, in- cluding anorexia, nausea, and general fatigue. Various mechanisms have been implicated in the etiology of cancer cachexia, and several studies have shown that cachexia associated with advanced cancer is associated with an increase in plasma cytokine levels. 1–3 Tumor necrosis factor (TNF)-α, interleukin (IL)-1, interferon (IFN)-γ, and IL-6 may play a role in many of the changes observed in cancer cachexia, including loss of body weight, loss of appetite, and induction of acute-phase proteins. 4 It has also been reported that the intraperitoneal injection of IL-1β decreases food intake and induces weight loss in mice. 5 Several gastrointestinal hormones may regulate food intake and energy balance by affecting the arcuate nucleus of the hypothalamus, which mediates changes in energy expenditure and appetite. Leptin is a peptide member of the cytokine receptor family and is produced primarily by fat cells. Leptin regulates fat mass by decreasing food intake (through decreasing the level of neuropeptide Y in the hypothalamus) and increasing resting energy expenditure, 6 and the administration of recombinant leptin has been shown to decrease food intake and increase energy expen- diture. 7,8 Additionally, Aleman et al. 9 found that in lung cancer patients with weight loss, circulating leptin concen- trations were not elevated but were inversely related to the severity of the inflammatory response. Serum leptin con- centrations in patients with advanced lung cancer depend only on the total amount of fat. Ghrelin is a 28-amino acid peptide that is secreted mainly from the stomach. It was first isolated in 1999 as an endog- enous ligand for the growth hormone (GH) secretagogue receptor (GHS-R). 10 In rodents 11 and humans, 12 several Received: August 17, 2007 / Accepted: October 24, 2008 Abstract Background. Cancer cachexia, a catabolic state character- ized by weight loss, occurs frequently in patients with ter- minal-stage neoplastic diseases. Gastrointestinal hormones and cytokines may be associated with anorexia and wasting in cancer cachexia. Methods. This study aimed to examine the mechanism of anorexia in cachectic patients through a prospective investigation of plasma cytokines, ghrelin, and leptin in 16 cachectic patients with cancer of the digestive organs and 10 healthy volunteers. Results. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1 receptor antagonist (IL-1Ra), and ghrelin levels were significantly higher in cachectic cancer patients than in the healthy volunteers, whereas leptin was significantly lower in the cachectic cancer patients. Plasma leptin levels and cytokine levels (TNF-α and IL-6) correlated significantly with body mass index (BMI), but plasma ghrelin levels did not correlate with BMI or with the grade of symptoms. Conclusion. Neither weight loss nor the grade of symptoms seemed to be directly associated with the increase in ghrelin levels. Hence, it is considered that the increase in ghrelin levels cannot simply be explained by an increase in ghrelin secretion, suggesting that other mechanisms, such as the decreased inactivation of ghrelin, may also play a role. Further studies are needed to clarify the mechanisms of the increase in ghrelin levels. Additionally, the changes in plasma cytokines (TNF-α and IL-6) and leptin in cachectic cancer patients suggest that these molecules may be useful markers for the evaluation of cancer cachexia.