Abstract B36: Induction of IL-6 by breast cancer chemotherapy mediates loss of fat-free lean body mass in tumor-free mice by decreasing systemic IGF-1

Abstract

Abstract Aims: Cancer patients treated with cytotoxic chemotherapy often experience changes in body composition that occur independent of changes in food intake or physical activity. These changes may impact physical functioning and quality of life. Interleukin-6 (IL-6), an inflammatory cytokine that is up-regulated in cancer patients treated with cytotoxic chemotherapies, plays an important role in the regulation of body composition. The purpose of this study was to determine the role of IL-6 in the regulation of systemic insulin-like growth factor I (IGF-1) levels and treatment induced changes in body composition using a pre-clinical model. Methods: Changes in body composition and systemic IGF-1 levels were assessed in IL-6−/− mice and their wild type counterparts before and after 4 cycles of cytoxan-adriamycin-5-fluorouracil (CAF) a common adjuvant breast cancer chemotherapy regimen. Daily food intake and physical activity were monitored throughout treatment. Results: We found that CAF decreased systemic IGF-1 production in an IL-6-dependent manner. Similar to cancer patients, CAF treatment in WT mice led to a reduction in fat free LBM and bone mass but not fat mass (FM). These changes occurred independently of food intake and level of physical activity. In contrast, IL-6 deficient mice were protected from the treatment induced loss of fat free LBM but not bone mass. Conclusions: These preclinical findings implicate IL-6 mediated reduction in systemic IGF-1 as a possible mechanism underlying the loss of fat free LBM in cancer patients undergoing cytotoxic chemotherapy. Based upon these pre-clinical findings, examination of these relationships in the clinical setting is warranted. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B36