Experimental study of the effect of IL-6 on cancer cachexia

Several cytokines, including IL-1, TNF, LIF and IL-6 have recently been proposed as cachexia inducers. We experimentally examined the participation of cytokines, particularly, IL-6, in cancer cachexia using the human digestive cancer cell lines MKN 28, MKN 45, MKN 74, Kato-III, OCUM-2M (gastric cancer), SW1990, Panc-1 (pancreatic cancer), and OCUG (gallbladder cancer). A high level of IL-6 was detected in the OCUG culture medium. Nude mice bearing OCUG tumor had reduced body weight even when the tumor was relatively small. Loss of both muscle and adipose tissue, anemia, hypoglycemia, and a high serum level of human IL-6 were observed in these mice. However, body weight recovered rapidly to the level of that of nontumor-bearing mice after resection of OCUG tumor. Antihuman IL-6 but not anti-murine IL-6 receptor antibodies significantly suppressed the development of cachexia as measured by various indicators of cachexia including loss of both muscle and adipose tissue, anemia and hypoglycemia, as well as weight loss. These results suggest that OCUG-bearing mice exhibited cancer cachexia mediated by IL-6, and that of OCUG cell line might be useful as a human digestive cancer cachexia model.