Induction of IL-6 by Cytotoxic Chemotherapy Is Associated With Loss of Lean Body and Fat Mass in Tumor-free Female Mice

Collin R. Elsea, Janet A. Kneiss, Lisa J. Wood

    Research output: Contribution to journalArticle

    7 Scopus citations

    Abstract

    Cancer patients treated with cytotoxic chemotherapy experience fatigue and changes in body composition that can impact physical functioning and quality of life during and after treatment. Interleukin-6 (IL-6) is associated with fatigue in cancer survivors and plays an important role in the regulation of body composition. The purpose of the present study was to determine the specific role of IL-6 in cyclophosphamide-doxorubicin-5-fluorouracil (CAF)-induced changes in fatigue, food intake, and body composition using mice lacking IL-6. Female wild-type (WT) and IL-6−/− mice were injected with four cycles of CAF or normal saline (NS) administered at 21-day intervals. Daily voluntary wheel-running activity (VWRA), used as a proxy for fatigue, and food intake were monitored daily up to 21 days after the fourth dose. Dual-energy X-ray absorptiometry (DEXA) was used to assess treatment-related changes in lean body mass (LBM), fat mass (FM), and bone mineral content (BMC). Patterns of change in fatigue and food intake did not differ between CAF-treated WT and IL-6−/− mice. However, a Genotype × Drug interaction was observed for LBM (p = 0.047) and FM (p = 0.035) but not BMC (p =.569). Whereas WT mice lost LBM and FM during CAF treatment, IL-6-deficient mice did not. Treatment-related decreases in levels of the anabolic hormone insulin-like growth factor-1 (IGF-1) may contribute to LBM and FM loss since CAF decreased IGF-1 levels in an IL-6-dependent manner. These findings implicate IL-6 and possibly IGF-1 in the regulation of body composition in breast cancer patients exposed to cytotoxic chemotherapy.

    Original languageEnglish (US)
    Pages (from-to)549-557
    Number of pages9
    JournalBiological research for nursing
    Volume17
    Issue number5
    DOIs
    StatePublished - Oct 8 2015

    Keywords

    • IL-6
    • body composition
    • cachexia
    • doxorubicin
    • fatigue

    ASJC Scopus subject areas

    • Research and Theory

    Fingerprint Dive into the research topics of 'Induction of IL-6 by Cytotoxic Chemotherapy Is Associated With Loss of Lean Body and Fat Mass in Tumor-free Female Mice'. Together they form a unique fingerprint.

  • Cite this