Abstract B35: Serum inflammatory biomarkers of acute and persistent fatigue in a preclinical breast cancer treatment model

Abstract

Abstract Aims: Cancer treatment related fatigue (CTRF) is a debilitating symptom of cancer chemotherapy. The acute CTRF that occurs during chemotherapy can become persistent lasting for weeks, month, or years after treatment has ended. Although, treatment-related increases in IL-1β and TNF-α have been implicated in CTRF, the role that these cytokines play in CTRF is unclear. The aim of this study was to determine the relationship between chemotherapy-induced IL-1β and TNF-α production and acute and persistent CTRF in a pre-clinical mouse model. Methods: Blood levels of IL-1β, TNF-α and several other inflammatory biomarkers were measured in acutely fatigued, non-fatigued, and persistently fatigued mice following administration of cytoxan-adriamycin-5-fluorouracil (CAF), a commonly used adjuvant chemotherapy regimen for the treatment of breast cancer, by assessing changes in voluntary wheel running activity as a proxy for fatigue. Results: Fatigued mice showed increased blood levels of IL-1β, TNF-α as well as several other inflammatory markers including, IL-5, IL-6, IL-7, IL-9, IP-10, G-CSF, KC, MCP-1 and MIP-1β. Importantly, serum levels of these fatigue associated biomarkers were not significantly increased in non-fatigued CAF treated mice. CAF-treated mice with persistent fatigue had elevated serum levels of IL-6, IL-17, and MIP-1α. Conclusions: This study advances the science of symptom management by providing evidence that treatment induced increases in IL-1β and TNF-α play a role in acute CTRF. Similar temporal analyses between serum inflammatory biomarkers in the clinical setting may lead to a better understanding of the role of immune dysfunction in the etiology of acute and persistent fatigue. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B35