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• W2048868684 abstract "Patients undergoing external beam radiation therapy (EBRT) for prostate cancer experience a progressive increase in fatigue which can affect physical functioning, and QOL. Treatment related fatigue can persist for months after treatment has ended. It has been suspected that this fatigue is the same as sickness syndrome, caused in large part by the systemic production of the pro-inflammatory cytokine TNF-α. Yet, whether localized EBRT, can cause a rise in systemic TNF-α and sickness syndrome is not known and is the focus of this study. To determine the effects of EBRT on sickness syndrome in mice, weight, food intake and wheel running activity were assessed in male C57BL/6 mice undergoing EBRT to the pelvis. Baseline average daily food intake, weight and activity level were measured over a two week period prior to EBRT. Twenty mice underwent EBRT under anesthesia to the pelvis using a fractionated dose of 2.84 Gy, 5 days per week for 24 fractions for a total dose of 68.2 Gy, thereby mimicking the clinical therapeutic dose. Twenty mice (controls) were treated in an identical manner but were not irradiated. The day after the last radiation dose, 10 mice from each group were sacrificed and liver levels of TNF-α mRNA were measured by quantitative real time PCR (qRT-PCR). Plasma levels of TNF-α were measured using a bead-based immunofluorescence assay. The remaining mice were monitored for a further 3 weeks, prior to sacrifice and tissue collection. Irradiated mice showed a progressive decline in body weight and daily activity compared to controls. Food intake during treatment was no different between the two groups. At the end of treatment, plasma levels of TNF-α and liver TNF-α mRNA levels were significantly elevated compared to control mice. Three weeks after the last treatment dose activity level and body weight had still not returned to pre-treatment levels. At this time point plasma levels of TNF-α were significantly increased in mice administered RT relative to controls. Study findings demonstrate that localized EBRT can induce a systemic TNF-α response and sickness syndrome in mice that persists weeks after treatment has ended. Further experiments using TNF-deficient mice will allow us to determine the role of TNF-α in sickness syndrome induced by EBRT. This information may lead to targeted strategies aimed at blocking TNF-α in men undergoing localized EBRT with the aim of reducing treatment related fatigue thereby improving QOL." @default.
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• W2048868684 date "2008-09-01" @default.
• W2048868684 modified "2023-09-26" @default.
• W2048868684 title "Pelvic Irradiation Induces a Systemic TNF-α Response and Sickness Syndrome in Mice: Implications for Cancer Treatment Related Fatigue" @default.
• W2048868684 doi "https://doi.org/10.1016/j.ijrobp.2008.06.609" @default.
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