Article

Inflammatory responses to psychological stress in fatigued breast cancer survivors: Relationship to glucocorticoids

Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience at UCLA, 300 UCLA Medical Plaza, Room 3306, Box 957076 Los Angeles, CA 90095-7076, USA.
Brain Behavior and Immunity (Impact Factor: 6.13). 03/2007; 21(3):251-8. DOI: 10.1016/j.bbi.2006.08.001
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ABSTRACT Fatigue is a common problem following cancer treatment and our previous studies suggest that a chronic inflammatory process might contribute to cancer-related fatigue. However, immune responses to challenge have not yet been evaluated among individuals with cancer-related fatigue, and it is not known what mechanisms drive increased levels of inflammatory markers in fatigued cancer survivors. We have previously reported that fatigued breast cancer survivors show a blunted cortisol response to an experimental psychological stressor. In this report, we focus on inflammatory responses to this stressor and their relationship to circulating glucocorticoids and cellular sensitivity to glucocorticoid inhibition. Relative to non-fatigued control survivors, participants experiencing persistent fatigue showed significantly greater increases in LPS-stimulated production of IL-1beta and IL-6 following the stressor (Group x Time interaction: p<.05). Fatigued participants did not show any difference in cellular sensitivity to cortisol inhibition of cytokine production, but they did show significantly less salivary cortisol increase in the aftermath of the stressor. Moreover, blunted cortisol responses were associated with significantly increased production of IL-6 in response to LPS stimulation (p<.05). These data provide further evidence of enhanced inflammatory processes in fatigued breast cancer survivors and suggest that these processes may stem in part from decreased glucocorticoid response to stress.

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    • "It also plays a role in the acute phase response and systemic inflammation and is involved in the creation of new blood vessels, the regulation of cell differentiation, and programmed cell death (Kindt et al., 2006). In serum and plasma, TNF-a has been shown to increase in response to a TSST (Altemus et al., 2001; Bower et al., 2007), an anger-recall task (Suarez et al., 2006), a speech task (Ackerman et al., 1998), and mental arithmetic, Stroop, and public speech tasks (Heesen et al., 2002). Consistently high levels of TNF-a are often interpreted as evidence of dysregulation and have been shown to be related to a variety of chronic diseases, including Alzheimer's disease (Minagar et al., 2002), major depression (Khairova et al., 2009; Tuglu et al., 2003), certain cancers (Balkwill, 2006), multiple sclerosis (Minagar et al., 2002), cardiovascular diseases (Cesari et al., 2003; Stoner et al., 2013), and general frailty (Hubbard et al., 2009). "
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    ABSTRACT: There is burgeoning interest in the ability to detect inflammatory markers in response to stress within naturally occurring social contexts and/or across multiple time points per day within individuals. Salivary collection is a less invasive process than current methods of blood collection and enables intensive naturalistic methodologies, such as those involving extensive repeated measures per day over time. Yet the reliability and validity of saliva-based to blood-based inflammatory biomarkers in response to stress remains unclear. We review and synthesize the published studies that have examined salivary markers of inflammation following exposure to an acute laboratory stressor. Results from each study are reviewed by analyte (IL-1β, TNF-α, IL-6, IL-2, IL-4, IL-10, IL-12, CRP) and stress type (social-cognitive and exercise-physical), after which methodological issues and limitations are addressed. Although the literature is limited, several inflammatory markers (including IL-1β, TNF-α, and IL-6) have been reliably determined from saliva and have increased significantly in response to stress across multiple studies, with effect sizes ranging from very small to very large. Although CRP from saliva has been associated with CRP in circulating blood more consistently than other biomarkers have been associated with their counterparts in blood, evidence demonstrating it reliably responds to acute stress is absent. Although the current literature is presently too limited to allow broad assertion that inflammatory biomarkers determined from saliva are valuable for examining acute stress responses, this review suggests that specific targets may be valid and highlights specific areas of need for future research.
    Brain Behavior and Immunity 09/2014; 44. DOI:10.1016/j.bbi.2014.08.008 · 6.13 Impact Factor
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    • "The disarray in sympathetic and parasympathetic responses can also activate the pro-inflammatory cytokine network (Fagundes et al., 2011). High levels of pro-inflammatory cytokines (IL-6, IL-1b) (Wratten et al., 2004; Bower et al., 2007) and activated immune cells (CD4+ T lymphocytes ) have been observed in individuals reporting fatigue while receiving cancer therapy (Bower et al., 2007). The overexpression of the SNCA gene observed in this study indicates that neuroinflammatory mechanisms may play a role in the development of fatigue in this population, considering Table 2 Clinical and demographic characteristics of the samples. "
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    Brain Behavior and Immunity 09/2012; 27. DOI:10.1016/j.bbi.2012.09.009 · 6.13 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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