| First Author | McDonald TL | Year | 2016 |
| Journal | Radiat Res | Volume | 185 |
| Issue | 1 | Pages | 4-12 |
| PubMed ID | 26720802 | Mgi Jnum | J:329085 |
| Mgi Id | MGI:6880589 | Doi | 10.1667/RR14072.1 |
| Citation | McDonald TL, et al. (2016) Localized External Beam Radiation Therapy (EBRT) to the Pelvis Induces Systemic IL-1Beta and TNF-Alpha Production: Role of the TNF-Alpha Signaling in EBRT-Induced Fatigue. Radiat Res 185(1):4-12 |
| abstractText | 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-1beta 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-1beta 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 wild-type counterparts. Taken together our data demonstrate that a clinically relevant localized irradiation of the pelvis induces a systemic IL-1beta and TNF-alpha response and sickness behavior in mice, but the TNF-alpha signaling pathway alone does not independently mediate these effects. |
