Involvement of human interleukin 6 in experimental cachexia induced by a human uterine cervical carcinoma xenograft

In this experimental study, the authors examined the role of various cytokines in the development of cancer cachexia. After in vitro culture and selection of a single clone of tumor cells, a growing uterine cervical carcinoma from human origin was implanted subcutaneously in nude mice. Body weight and tumor volume were measured throughout the study period; tissue wasting was assessed by weighing the gastrocnemius muscle and the peri-ovarian white adipose tissue. Serum and tumor cytokine concentrations, including human G-CSF, murine and human tumor necrosis factor (TNF)- proportional, variant, IFN-gamma, interleukin (IL)-1 proportional, variant and IL-6, were determined by ELISA at the end of the study. Two months after implantation, the tumor (4% of carcass weight) induced severe loss of adipose tissue (-95%) and muscle mass (-49%). Human IL-6 (0.38 +/- 0.19 ng/ml) and human G-CSF were detected in the serum and the tumor tissue of these animals; none of the cytokines of murine origin was detected in the serum, except IL-6 (0.14 +/- 0.05 ng/ml). Treatment with neutralizing anti-human IL-6 antibodies reduced plasma IL-6 and G-CSF levels and significantly increased host carcass weight (16%) and fat mass (353%). The authors conclude that human IL-6 produced by tumor cells is an essential mediator of cachexia in this model.