Bower, J. E. Cancer-related fatigue: links with inflammation in cancer patients and survivors. Brain Behav. Immun. 21, 863-871

UCLA Department of Psychology, 1285 Franz Hall, Los Angeles, CA 90095-1563, USA.
Brain Behavior and Immunity (Impact Factor: 5.89). 11/2007; 21(7):863-71. DOI: 10.1016/j.bbi.2007.03.013
Source: PubMed


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 · 2.98 Impact Factor
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    • "Fatigue is a common symptom among individuals living with chronic illness, and there is growing evidence from animal models (Harrington, 2012) and adults with chronic illness (Bower et al., 2013; Miaskowski et al., 2010) that fatigue is associated with inflammation and cytokine activity in plasma. Tumor necrosis factor – alpha (TNF-α)(Aouizerat et al., 2009; Bower et al., 2013; Fung et al., 2013; Jim et al., 2012), interleukin 6 (IL6)(Inagaki et al., 2013; Rohleder et al., 2012; Schrepf et al., 2013; Schubert et al., 2007; Starkweather, 2013), and IL-1 beta (IL-1β) (Bower, 2007; Saligan and Kim, 2012; van Zuiden et al., 2012) exhibit the strongest relationships with fatigue in prior studies, although other cytokinefatigue associations have also been reported (Bower et al., 2011; Liu et al., 2012; Piraino et al., 2012) and still other studies have yielded contradictory results (Cameron et al., 2012; Dirksen et al., 2013; Geinitz et al., 2004; Hamre et al., 2013). Both cytokine plasma concentrations and polymorphisms are implicated in fatigue, yet the nature of these relationships remains poorly understood. "
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    ABSTRACT: Fatigue has been associated with inflammation and cytokine activity among adults, but this relationship has not been evaluated among adults living with HIV. Diurnal patterns of fatigue have been previously identified in adults with HIV/AIDS. Thus, the purpose of this study was to describe these fatigue patterns in relation to cytokine plasma concentrations and gene polymorphisms. A convenience sample of 317 adults living with HIV/AIDS completed a measure of fatigue in the morning and evening for three consecutive days; participants reporting low levels of both morning and evening fatigue (n=110) or high levels of fatigue in the morning and evening (n=114) were included in the analysis, resulting in a final sample of 224 adults (151 men, 55 women, and 18 transgender). Plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB-1 and -2), and tumor necrosis factor alpha (TNFA). Demographic and clinical variables were evaluated as potential covariates. Controlling for genomic estimates of ancestry and self-reported race/ethnicity and gender, the high fatigue pattern was associated with five single nucleotide polymorphisms (SNPs): IL1B rs1071676 and rs1143627, IL4 rs2243274, and TNFA rs1800683 and rs1041981. The IL1B and TNFA polymorphisms were not associated with plasma levels of IL-1β or TNFα, respectively. This study strengthens the evidence for an association between inflammation and fatigue. In this chronic illness population, the cytokine polymorphisms associated with high levels of morning and evening fatigue provide direction for future personalized medicine intervention research.
    Brain Behavior and Immunity 08/2014; 40. DOI:10.1016/j.bbi.2014.02.017 · 5.89 Impact Factor
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    • "Furthermore, single nucleotide polymorphism in the promoter region of the cytokines ILB -511 C>T (rs 16944), IL6 -174 G>C (rs1800795) and TNF -308 G>A (rs 1800629) suggests an inflammatory basis for fatigue [25]. Already in 2007, Bower JE [26] summarized emerging evidence that inflammatory processes my be involved in CRF during and after treatment and his group recently examined the hypothesis that CRF is driven by activation of the pro-inflammatory cytokine network [27]. The hypothesis driven view that CRF is related to inflammatory processes [28] or to the serotonin, to the vagal-afferent activation, to the anemia and to the adenosine triphosphate hypotheses [29] has a history since midth of 2007. "
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    ABSTRACT: Background: Cancer-related fatigue (CRF) affects a majority of patients (pts) with symptoms lasting up to several years after finishing therapy. These symptoms lead to decreased health related quality of life. Fatigue during treatment for colorectal cancer is common, but poorly understood and can affect compliance with post-surgical cancer therapy. We examined the fatigue levels during first-line chemo- or radio-chemotherapy protocols, which were supported by a pharmaceutical mistletoe preparation (Iscador(®)Qu) (181patients). We compared the outcome to a parallel control group (143 patients), which did not receive this supportive care treatment. Methods: The medical records of 324 patients with non-metastasized colorectal cancer (UICC stage I-III), which were obtained from hospitals and resident physicians, were assessed. The documented treatment decision by chemo- or radio-chemotherapy supported by mistletoe interventions was followed for a median treatment period of 8.6 months. During the post-surgical treatment period the patients were diagnosed twice for the presence of fatigue symptoms by structural interviews carried out by physicians. Results: At the end of the median treatment period, 16/181 patients (8.8%) were diagnosed with CRF in the supportive care group and 86/143 (60.1%) in the chemo- or radio-chemotherapy group without supportive mistletoe medication. Multivariable-adjusted ORs provided evidence for a chance to improve CRF by supportive mistletoe medication compared to chemo- or radio-chemotherapy alone over the time of treatment. The OR = 10.651 (95% CI 5.09-22.28; p < 0.001) declined from the first visit to OR = 0.054 (95 CI 0.02-0.13; p < 0.001) at the end of therapy. Furthermore, 14 confounding factors for risk assessment of CRF were compared by means of forest plots. It turned out that the hospital versus office-based treatment and the co-morbidity/inflammation represent independent but important determinants for fatigue levels. Conclusion: The clinically used mistletoe medication (Iscador(®)Qu) is the first candidate to be included in a supportive care modus into chemo- or chemo-radiotherapy protocols for colorectal patients to improve CRF without discernable toxicities.
    04/2014; 13(2). DOI:10.2174/1871528113666140428103332
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