title: 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.
abstract: 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-1β and TNF-α 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-1β and TNF-α. In a follow-up experiment, we used TNF-α-deficient mice to further delineate the role of TNF-α signaling in EBRT-induced sickness behavior. EBRT-induced changes in fatigue, food intake and body weight were no different between TNF-α 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-1β and TNF-α response and sickness behavior in mice, but the TNF-α signaling pathway alone does not independently mediate these effects.
authors.affiliation: a  Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon; and.
authors.forename: Tasha L
authors.initials: TL
authors.lastname: McDonald
authors.affiliation: a  Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon; and.
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Hung
authors.affiliation: a  Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon; and.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Thomas
authors.affiliation: b  Amelia Peabody Professor for Nursing Research, MGH Institute of Health Professions, School of Nursing, Boston, Massachusetts.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Wood
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects*; D001835:Body Weight / Q000528:radiation effects; D004435:Eating / Q000528:radiation effects; D005221:Fatigue / Q000209:etiology / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010388:Pelvis / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000150:complications / Q000532:radiotherapy; D011832:Radiation Injuries / Q000209:etiology / Q000503:physiopathology*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D015398:Signal Transduction / Q000528:radiation effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha