title: Effects of 5-fluorouracil chemotherapy on fatigue: role of MCP-1.
abstract: Chemotherapy has been known to cause severe side effects, including fatigue. While the mechanisms for chemotherapy induced fatigue (CIF) are likely to be multi-factorial in origin, it is thought that inflammation and anemia may play a role. The purpose of this study was to examine the effect of chemotherapy on fatigue in mice, and further, to begin to determine if inflammation and anemia may contribute to this response. For experiment 1, C57BL/6 mice were assigned to: vehicle (PBS), low (20 mg/kg), medium (40 mg/kg), or high (60 mg/kg) doses of 5-fluorouracil (5-FU). Voluntary physical activity (PA) was measured throughout the treatment period (day 1-5) as well as during the recovery period (day 6-14). In experiment 2, we examined the effects of 5-FU (60 mg/kg) on the inflammatory mediator MCP-1 and on markers of anemia (RBC, Hct and Hb). Finally, using MCP-1(-/-) mice we examined the role of MCP-1 on CIF (experiment 3). 5-FU reduced voluntary PA in a dose response manner (p<0.05). Plasma MCP-1 was increased following 5-FU treatment on both days 5 (p=0.10) and 14 (p<0.05). In addition, RBCs, Hct and Hb were reduced with 5-FU on days 5 and 14 (p<0.05). Both C57BL/6 and MCP-1(-/-) mice saw similar decrements in PA through the duration of the treatment period (days 1-5), however the MCP-1(-/-) mice recovered much earlier than wildtype mice. This study provides evidence of the dose response effect of a standard chemotherapy agent on fatigue and demonstrates a potential role of MCP-1 and presumably inflammation, and anemia.
authors.affiliation: Department of Health and Kinesiology, Texas A&M University, Kingsville, TX 78363, USA. sara.mahoney@tamuk.edu
authors.forename: S E
authors.initials: SE
authors.lastname: Mahoney
authors.forename: J M
authors.initials: JM
authors.lastname: Davis
authors.forename: E A
authors.initials: EA
authors.lastname: Murphy
authors.forename: J L
authors.initials: JL
authors.lastname: McClellan
authors.forename: B
authors.initials: B
authors.lastname: Gordon
authors.forename: M M
authors.initials: MM
authors.lastname: Pena
mesh_terms: D000740:Anemia / Q000209:etiology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000276:immunology; D018932:Chemokine CCL2 / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005221:Fatigue / Q000209:etiology* / Q000276:immunology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000276:immunology; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000276:immunology*
chemical_list: D000964:Antimetabolites, Antineoplastic; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D005472:Fluorouracil