Cancer-related fatigue: Links with inflammation in cancer patients and survivors

UCLA Department of Psychology, 1285 Franz Hall, Los Angeles, CA 90095-1563, USA.
Brain Behavior and Immunity (Impact Factor: 6.13). 11/2007; 21(7):863-71. DOI: 10.1016/j.bbi.2007.03.013
Source: PubMed

ABSTRACT Fatigue is one of the most common and distressing side effects of cancer and its treatment and may persist long after successful treatment completion. Emerging evidence suggests that inflammatory processes may be involved in cancer-related fatigue both during and after treatment. In this review, we consider the evidence for an association between inflammation and fatigue in cancer patients and survivors. Further, we identify potential mechanisms for persistent inflammation, focusing on the HPA axis. Risk factors and treatments for cancer-related fatigue are also discussed.

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    • "Recent evidence from rodent models indicates that inflammatory cytokines within the CNS are associated with symptoms of fatigue, such as decreased voluntary wheel running activity (Carmichael et al., 2006). Although a link between inflammation and fatigue in cancer patients has been suggested (Bower, 2007), no clear connection between CNS inflammation and CRF has been reported. The aim of this study was to discriminate between loss of muscle mass and depressed mood in a mouse model of CRF. "
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    ABSTRACT: Cancer patients frequently suffer from fatigue, a complex syndrome associated with tiredness and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, escalates during treatment, and can persist for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. We have previously shown that increased pro-inflammatory cytokine expression in the brain contributes to depressive- and fatigue- like behaviors in a mouse model of CRF. Inflammatory cytokines increase activity of indoleamine 2,3-dioxygenase (IDO) and kynurenine 3-monooxygenase (KMO), which competitively reduce serotonin synthesis. Reduced serotonin availability in the brain and increased production of alternative neuroactive metabolites of tryptophan are thought to contribute to the development of depression and fatigue. The purpose of this study was to determine the effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on brain cytokines and behavioral measures of fatigue and depression in tumor-bearing mice. Here we show that tumor growth increased brain expression of pro-inflammatory cytokines and KMO. Treatment with fluoxetine had no effect on tumor growth, muscle wasting, fatigue behavior, or cytokine expression in the brain. Fluoxetine, however, reduced depressive-like behaviors in tumor bearing mice. In conclusion, our data confirm that increased brain expression of pro-inflammatory cytokines is associated with tumor-induced fatigue and depressive-like behavior. However, it is possible to separate the effects of tumor growth on mood and fatigue-like behaviors using SSRI's such as fluoxetine. Copyright © 2014. Published by Elsevier Inc.
    Physiology & Behavior 12/2014; 140. DOI:10.1016/j.physbeh.2014.12.045 · 3.03 Impact Factor
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    • "We used descriptive statistics and structural equation modeling (SEM) to analyze the data. The SEM analysis was inspired by Bower's (2007) model, which describes a potential associations among cancer and cancer treatment, inflammation, and cancer-related fatigue. In that model, cancer and its treatment activate the inflammatory network which, in turn, leads to symptoms of fatigue. "
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    ABSTRACT: Sickness behavior is a cluster of symptoms that occur as a response to an infection and alterations in the inflammatory response. Under normal circumstances, sickness behavior is fully reversible once the pathogen has been cleared. Aging and chronic illness such as heart failure are associated with enhanced inflammatory activity that lasts for a long duration and no longer represents an adaptive response. The aim of this study was to explore whether inflammation mediates the relationship between impaired cardiac function and a symptom cluster including anhedonia, fatigue, and sleepiness, which might represent sickness behavior in community-dwelling elders. Structural equation modeling (SEM) showed that the factor impaired cardiac function (i.e., N-terminal fragment of pro-brain natriuretic peptide, left ventricular ejection fraction, and the heart failure medications angiotensin converting enzyme inhibitor, angiotensin receptor blockade, β-blocker, and diuretics) was associated with both inflammation (i.e., C-reactive protein; β = .26) and the symptom cluster (β = .31). Inflammation had a significant direct, but smaller, association with the symptom cluster (β = .21). By this pathway, inflammation also mediated an indirect association between impaired cardiac function and the symptom cluster (β = .05). Including creatinine, blood glucose, ischemic heart disease, previous and current tumor, respiratory disease, age, and body mass index in the SEM model did not change these associations. Our results imply that some aspects of the symptom panorama in elderly individuals with impaired cardiac function or heart failure could represent sickness behavior.
    Biological Research for Nursing 11/2012; 16(1). DOI:10.1177/1099800412466170 · 1.34 Impact Factor
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    • "All models that try to explain the cause and development of fatigue assume that there are complex, multicausal processes that create the disability. Suggested pathophysiological factors include a dysregulation of inflammatory cytokines, interruption of the regulatory circuits of the hypothalamus, changes in the serotonin system of the central nervous system, and interruption of the circadian secretion of melatonin and of the circadian rhythm [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]. Among the various treatment strategies, that is, exercise, psychosocial support, stress management, nutrition, sleep regulation, and restorative therapy [34], physical activity was identified as important particularly for patients with advanced stages of cancer to attenuate anxiety, depression, stress, and fatigue [35]. "
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    ABSTRACT: Background. Researchers aimed at systematically reviewing and meta-analyzing the effectiveness of yoga interventions for fatigue. Methods. PubMed/Medline was searched until January 2012 for controlled clinical studies. Two reviewers independently extracted the data. The methodological quality of the studies was assessed. A meta-analysis was performed. Results. Nineteen clinical studies (total n = 948) were included in this review. Investigated yoga styles included Hatha, Iyengar, Asanas, Patanjali, Sahaja, and Tibetan yoga. Participants were suffering from cancer, multiple sclerosis, dialysis, chronic pancreatitis, fibromyalgia, asthma, or were healthy. Yoga had a small positive effect on fatigue (SMD = 0.27, 59% CI = 0.23–0.31). Seven studies received 4 points on the Jadad score. There were baseline differences in at least 5 studies. Conclusion. Overall, the effects of yoga interventions on fatigue were only small, particularly in cancer patients. Although yoga is generally a safe therapeutic intervention and effective to attenuate other health-related symptoms, this meta-analysis was not able to define the powerful effect of yoga on patients suffering from fatigue. Treatment effects of yoga could be improved in well-designed future studies. According to the GRADE recommendations assessing the overall quality of evidence, there is a moderate effect of the confidence placed in the estimates of the effects discussed here.
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