Fatigue and proinflammatory cytokine activity in breast cancer survivors.
OBJECTIVE
Fatigue is a common problem among cancer patients and survivors, yet the mechanisms underlying the occurrence and persistence of this symptom are not known. Activation of the immune system may evoke feelings of fatigue, which are mediated by proinflammatory cytokines. We examined whether fatigued breast cancer survivors would show elevations in proinflammatory cytokines and markers of cytokine activity compared with nonfatigued survivors. Differences in lymphocyte subsets, cortisol, and behavioral symptoms associated with proinflammatory cytokines were also assessed.


METHODS
Forty breast cancer survivors (20 fatigued, 20 nonfatigued) provided blood samples at visits scheduled to control for diurnal variability. Cytokines, soluble markers of cytokine activity, and cortisol were measured by immunoassay and lymphocyte subsets by flow cytometry. Participants also completed questionnaires measuring demographic, medical, and behavioral variables.


RESULTS
Fatigued breast cancer survivors had significantly higher serum levels of several markers associated with proinflammatory cytokine activity than nonfatigued survivors, including interleukin-1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor type II (sTNF-RII), and neopterin. They were also more likely to report behavioral problems that co-occur with fatigue in the context of immune activation. Fatigued survivors had significantly lower serum levels of cortisol than the nonfatigued group as well as differences in two lymphocyte populations.


CONCLUSIONS
Fatigued breast cancer survivors showed elevations in serum markers associated with proinflammatory cytokine activity an average of 5 years after diagnosis. Results suggest mechanisms through which enduring immune activation may occur, including alterations in cortisol and in lymphocyte subsets.
Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center, University of California, Los Angeles 90095-6900, USA. jbower@ucla.edu
Julienne E
JE
Bower
Patricia A
PA
Ganz
Najib
N
Aziz
John L
JL
Fahey
D001943:Breast Neoplasms / Q000401:mortality* / Q000523:psychology*; D002940:Circadian Rhythm / Q000502:physiology; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D000068800:Etanercept; D005221:Fatigue / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000378:metabolism; D008875:Middle Aged; D019798:Neopterin / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007074:Immunoglobulin G; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019798:Neopterin; D000068800:Etanercept; D006854:Hydrocortisone