Levels of circulating interleukin-1 receptor antagonist and C-reactive protein in long-term survivors of testicular cancer with chronic cancer-related fatigue

Abstract

Low-grade inflammatory responses may be related to the pathogenesis of cancer-related fatigue (CRF). We investigated circulating levels of various inflammatory markers in relation to chronic CRF (6 month duration) in Norwegian long-term survivors of testicular cancer (TCSs). We compared 92 TCSs with chronic CRF (cases) to 191 TCS without (controls) at median age 45 years (range 23-73), and median 11 years post-treatment (range 5-20). Chronic CRF was defined using the Fatigue Questionnaire, while plasma concentrations of cytokines and serum CRP were determined by various immunoassays. Higher levels of interleukin-1 receptor antagonist (IL-1ra) (p=.002) and C-Reactive protein (CRP) (p=.036) were found in cases compared to controls. No differences were observed for interleukin-6 (IL-6), soluble Tumor Necrosis Factor Receptor type 1 (sTNF-R1) or neopterin. Both IL-1ra and CRP were correlated with physical but not with mental fatigue. In logistic regression analyses IL-1ra and CRP explained 3.5% and 2.8%, respectively, of the variance in chronic CRF. Single adjustments for depression, anxiety and neuroticism each raised the models' explained variance to approximately 35%. Those factors did not significantly alter the relationship between chronic CRF and IL-1ra/CRP. BMI and smoking emerged as possible confounding factors. These results indicate that chronic CRF in TCSs is associated with higher levels of circulating IL-1ra and CRP, possibly mediated by physiological morbidity. Hence, the findings lend some support to the hypothesis that low-grade inflammatory processes are involved in the pathogenesis of chronic CRF in cancer survivors.