期刊
RADIATION RESEARCH
卷 185, 期 1, 页码 4-12出版社
RADIATION RESEARCH SOC
DOI: 10.1667/RR14072.1
关键词
-
资金
- National Institute for Nursing Research [R21NR010363]
Prostate cancer patients undergoing localized external beam radiation therapy (EBRT) can experience a progressive increase in fatigue, which can affect physical functioning and quality of life. The purpose of this study was to develop a mouse EBRT prostate cancer treatment model with which to determine the role of pro-inflammatory cytokines in the genesis of EBRT-related fatigue. We assessed voluntary wheel-running activity (VWRA) as a proxy for fatigue, food intake and body weight in male C57BL/6 mice undergoing EBRT to the pelvis. In the first experiment, anesthetized male C57BL/6 mice underwent fractionated EBRT to the pelvis for a total dose of 68.2 Gy, thereby mimicking a clinically relevant therapeutic dose and frequency. The day after the last treatment, levels of IL-1 beta and TNF-alpha in plasma along with mRNA levels in liver, colon and whole brain were measured. EBRT-induced fatigue resulted in reduced body weight, diminished food intake, and increased plasma and tissue levels of IL-1 beta and TNF-alpha. In a follow-up experiment, we used TNF-alpha-deficient mice to further delineate the role of TNF-alpha signaling in EBRT-induced sickness behavior. EBRT-induced changes in fatigue, food intake and body weight were no different between TNF-alpha deficient mice and their wildtype counterparts. Taken together our data demonstrate that a clinically relevant localized irradiation of the pelvis induces a systemic IL-1 beta and TNF-alpha response and sickness behavior in mice, but the TNF-alpha signaling pathway alone does not independently mediate these effects. (C) 2016 by Radiation Research Society
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