Fatigue and sleep quality are associated with changes in inflammatory markers in breast cancer patients undergoing chemotherapy

Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093-0733, USA.
Brain Behavior and Immunity (Impact Factor: 5.89). 03/2012; 26(5):706-13. DOI: 10.1016/j.bbi.2012.02.001
Source: PubMed


Fatigue and sleep disturbances are two of the most common and distressing symptoms reported by cancer patients. Fatigue and sleep are also correlated with each other. While fatigue has been reported to be associated with some inflammatory markers, data about the relationship between cancer-related sleep disturbances and inflammatory markers are limited. This study examined the relationship between fatigue and sleep, measured both subjectively and objectively, and inflammatory markers in a sample of breast cancer patients before and during chemotherapy. Fifty-three women with newly diagnosed stage I-III breast cancer scheduled to receive at least four 3-week cycles of chemotherapy participated in this longitudinal study. Fatigue was assessed with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and objective sleep was measured with actigraphy. Three inflammatory markers were examined: Interleukin-6 (IL-6), Interleukin-1 receptor antagonist (IL-1RA) and C-reactive protein (CRP). Data were collected before (baseline) and during cycle 1 and cycle 4 of chemotherapy. Compared to baseline, more fatigue was reported, levels of IL-6 increased and IL-1RA decreased during chemotherapy. Reports of sleep quality remained poor. Mixed model analyses examining changes from baseline to each treatment time point revealed overall positive relationships between changes in total MFSI-SF scores and IL-6, between changes in total PSQI scores and IL-6 and IL-1RA, and between total wake time at night and CRP (all p's<0.05). These relationships suggest that cancer-related fatigue and sleep disturbances may share common underlying biochemical mechanisms.

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    • "This is not the first study to attempt to correlate serum cytokine levels with fatigue in patients receiving cancer therapy [37], but the timing of serum collection in this study reflected a better understanding of cytokine kinetics. Older studies measured cytokine concentrations once a week on a set day, regardless of when the patient actually received EBRT [38]. This is problematic because peak serum levels of IL-1b, TNF-a and IL-6 occur at 1–3 h post immune challenge [39]. "
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    ABSTRACT: Background and purpose: Mechanisms of fatigue reported during radiotherapy are poorly defined but may include inflammatory cytokines and/or sleep disturbances. This prospective, longitudinal, phase II study assessed fatigue, sleep, and serum cytokine levels during radiotherapy for early-stage prostate cancer (PCa). Material and methods: Twenty-eight men undergoing radiotherapy for early-stage PCa wore an Actiwatch Score to record fatigue level, sleep time, onset latency, efficiency and wake after sleep onset. Serum levels of IL-1α, IL-1β, TNF-α, IL-6, IL-8, IL-10 and VEGF were measured weekly during radiotherapy. Patient reported quality of life (QOL) metrics were collected before and after treatment. Linear mixed effects models examined trajectories across treatment weeks. Results: Fatigue increased across treatment weeks (P<.01), and fatigue was associated with decreased patient-reported QOL. Sleep efficiency increased across treatment weeks (rate of change over time=.29, P=.03), and sleep onset latency decreased (rate of change over time=.86, P=.06). IL-6 tended to increase during treatment (P=0.09), but none of the cytokine levels or sleep variables were significantly related to fatigue trajectories. Conclusions: Despite increased sleep efficiency across treatment weeks, fatigue significantly increased. Although IL-6 increased during the course of radiotherapy, cytokines levels were not associated with fatigue scores or sleep disturbance. Further studies are needed to define the mechanisms for fatigue during radiotherapy.
    Full-text · Article · Dec 2015 · Radiotherapy and Oncology
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    • "Levels of the proinflammatory cytokine interleukin-6 (IL-6) increase during cancer treatment. Researchers have suggested that this increase contributes to CRF (Liu et al., 2012; Wang et al., 2012). In individuals without cancer, endurance exercise training lowers resting levels of IL-6 (Reyes-Gibby et al., 2013), possibly by increasing the level of the anti-inflammatory cytokine IL-10 (Walsh et al., 2011). "
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    ABSTRACT: Cancer treatment is associated with decreased hemoglobin (Hb) concentration and aerobic fitness (VO2 max), which may contribute to cancer-related fatigue (CRF) and decreased quality of life (QoL). Endurance exercise may attenuate CRF and improve QoL, but the mechanisms have not been thoroughly investigated. Objectives. To (a) determine the feasibility of conducting an exercise intervention among women receiving treatment for breast cancer; (b) examine the effects of exercise on Hb and VO2 max and determine their association with changes in CRF and QoL; and (c) investigate changes in selected inflammatory markers. Methods. Fourteen women receiving chemotherapy for Stages I-II breast cancer were randomly assigned to exercise (n = 7) or usual care (n = 7). Women in the exercise group performed supervised, individualized treadmill exercise 2-3 times/week for the duration of chemotherapy (9-12 weeks). Data were collected 4 times over 15-16 weeks. Results. Recruitment rate was 45.7%. Sixteen women consented and 14 completed the trial, for a retention rate of 87.5%. Adherence to exercise protocol was 95-97%, and completion of data collection was 87.5-100%. Exercise was well tolerated. VO2 max was maintained at prechemotherapy levels in exercisers but declined in the usual-care group (p < .05). Hb decreased (p < .001) in all participants as they progressed through chemotherapy. Exercise did not have significant effects on CRF or QoL. Changes in inflammatory markers favored the exercise group. Conclusions. Exercise during chemotherapy may protect against chemotherapy-induced decline in VO2 max but not Hb concentration. © The Author(s) 2014.
    Full-text · Article · Jan 2015 · Biological Research for Nursing
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    • "orexin, from lethargy and loss of response to several stimuli to agitation and hyper-responsiveness to the same stimuli. Likewise, poor sleep quality in patients after chemotherapy has been closely linked to their inflammatory markers [114]. In the post-chemotherapy brain, the pathogenesis of which involves excess TNF generation [115] and lowered orexigenic activity [116], i.c.v. "
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    ABSTRACT: The depth, pattern, timing and duration of unconsciousness, including sleep, vary greatly in inflammatory disease, and are regarded as reliable indicators of disease severity. Similarly, these indicators are applicable to the encephalopathies of sepsis, malaria, and trypanosomiasis, and to viral diseases such as influenza and AIDS. They are also applicable to sterile neuroinflammatory states, including Alzheimer's disease, Parkinson's disease, traumatic brain injury, stroke and type-2 diabetes, as well as in iatrogenic brain states following brain irradiation and chemotherapy. Here we make the case that the cycles of unconsciousness that constitute normal sleep, as well as its aberrations, which range from sickness behavior through daytime sleepiness to the coma of inflammatory disease states, have common origins that involve increased inflammatory cytokines and consequent insulin resistance and loss of appetite due to reduction in orexigenic activity. Orexin reduction has broad implications, which are as yet little appreciated in the chronic inflammatory conditions listed, whether they be infectious or sterile in origin. Not only is reduction in orexin levels characterized by loss of appetite, it is associated with inappropriate and excessive sleep and, when dramatic and chronic, leads to coma. Moreover, such reduction is associated with impaired cognition and a reduction in motor control. We propose that advanced understanding and appreciation of the importance of orexin as a key regulator of pathways involved in the maintenance of normal appetite, sleep patterns, cognition, and motor control may afford novel treatment opportunities.
    Full-text · Article · Mar 2014 · Journal of Neuroinflammation
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