Levels of circulating interleukin-1 receptor antagonist and C-reactive protein in long-term survivors of testicular cancer with chronic cancer-related fatigue.
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.
Orre
Ingrid J
IJ
Department of Biological and Medical Psychology, Faculty of Psychology, University of Bergen, Jonas Lies vei 91, Bergen, Norway. ingrid.orre@psybp.uib.no
Murison
Robert
R
Dahl
Alv A
AA
Ueland
Thor
T
Aukrust
Pål
P
Fosså
Sophie D
SD
D000328:Adult; D000368:Aged; D001007:Anxiety / Q000523:psychology; D002097:C-Reactive Protein / Q000378:metabolism*; D002908:Chronic Disease; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D003863:Depression / Q000523:psychology; D005221:Fatigue / Q000097:blood* / Q000209:etiology* / Q000523:psychology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D009497:Neurotic Disorders / Q000523:psychology; D011569:Psychiatric Status Rating Scales; D053573:Receptors, Interleukin-1 Type I / Q000037:antagonists & inhibitors*; D011795:Surveys and Questionnaires; D017741:Survivors; D047990:TNF Receptor-Associated Factor 1 / Q000097:blood; D013736:Testicular Neoplasms / Q000097:blood* / Q000150:complications* / Q000523:psychology; D055815:Young Adult
D015850:Interleukin-6; D053573:Receptors, Interleukin-1 Type I; D047990:TNF Receptor-Associated Factor 1; D019798:Neopterin; D002097:C-Reactive Protein; D003346:Corticotropin-Releasing Hormone