Inflammatory Disease as Chronic Stress

Department of Medicine, University of Bristol, United Kingdom.
Annals of the New York Academy of Sciences (Impact Factor: 4.38). 06/1998; 840(1):599-607. DOI: 10.1111/j.1749-6632.1998.tb09599.x
Source: PubMed


It is now established that communication between the CNS and the immune system is bidirectional, that endocrine factors can alter immune function and that immune responses can alter both endocrine and CNS responses. In many respects CNS and endocrine responses to acute inflammation are similar to the changes associated with acute stress exposure. In contrast, during chronic inflammation associated with adjuvant induced arthritis (AA), although circulating levels of corticosterone are increased, the peptidergic regulation of the hypothalamus is different from that seen during acute stress. As the disease progresses, a paradoxical reduction occurs in CRH mRNA in the paraventricular nucleus (PVN), whereas PVN AVP mRNA increases. These data suggest that there is increased expression of AVP mRNA within the CRH cells of the PVN with an increased emphasis on AVP regulation of HPA output. Additionally, HPA function is altered during chronic inflammation such that responses to psychological stress (i.e. restraint) are significantly dampened, while responses to further inflammatory challenges are maintained. These data suggest that alterations in PVN peptide colocalization may be important in regulating the progression of peripheral inflammatory responses and that the effects of inflammation on the hypothalamus alter stress-responsive systems. In addition to the AA model, we have similarly observed alterations in PVN peptide mRNA expression with disease onset in the murine MRL lpr/lpr and MRL +/+ model of SLE. Disease onset in murine SLE is spontaneous and does not rely on exogenous application of adjuvant; however, decreased levels of CRH in the PVN were observed from early disease onset in this animal model. It is suggested that alterations in CRH regulation in response to either acute or chronic inflammation may contribute as etiological factors to both psychiatric (i.e. neuropsychiatric SLE) and stress-related disease.

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    • "The loss of LCn-3FAs from the diet and cell membranes coincides with widespread stress and the rise of Western " lifestyle " diseases, characterized by chronic inflammation [26] [27]. There is little doubt that stress is an inflammatory state, mediated by proinflammatory cytokines and other inflammatory mediators [28] [29] [30] [31] [32] [33], but a missing link to this knowledge is that inflammation is influenced by food consumption [34]. The immune system is intrinsically linked to the digestive system as food contains potential pathogens, which may invade and threaten homeostasis [35]. "
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    ABSTRACT: The study was undertaken to estimate the size of the impact of n-3 fatty acids in psychological stress and the extent to which it is mediated via proinflammatory cytokines. Structural equation modeling (SEM) was used to analyze data from 194 healthy Australians. Biomarkers used were erythrocyte polyunsaturated fatty acids (docosahexaenoic acid (DHA) and arachidonic acid (AA)), ex-vivo stimulated secretion of proinflammatory cytokines (interleukins (IL-1 and IL-6), and tumor necrosis factor (TNF)). Stress was measured with the perceived stress scale (PSS-10), found to comprise three factors: Coping (items 4, 7, 5), Overwhelm (2, 10, 6 and 8), and Emotional (1, 9 and 3). This modeling demonstrated that the effects of DHA on coping are largely direct effects (0.26, t = 2.05 ) and were not significantly mediated via the suppression of proinflammatory cytokines. Future modeling should explore whether adding EPA to the model would increase the significance of the mediation pathways.
    Evidence-based Complementary and Alternative Medicine 01/2012; 2012(9438):209197. DOI:10.1155/2012/209197 · 1.88 Impact Factor
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    • "Future studies could evaluate whether the many ailments presently associated with chronic stress and/or disregulation of GCs in human populations (e.g. obesity, diabetes and rheumatoid arthritis) (Glaser and Kiecolt-Glaser, 2005; Shanks et al., 1998) occur in for animals in zoos, aquaria and captive breeding and translocation programs. "
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    ABSTRACT: Some species thrive in captivity but others exhibit extensive psychological and physiological deficits, which can be a challenge to animal husbandry and conservation as well as wild immunology. Here, we investigated whether captivity duration impacted the regulation of a key innate immune response, inflammation, of a common wild bird species, the house sparrow (Passer domesticus). Inflammation is one of the most commonly induced and fast-acting immune responses animals mount upon exposure to a parasite. However, attenuation and resolution of inflammatory responses are partly coordinated by glucocorticoid hormones, hormones that can be disregulated in captivity. Here, we tested whether captivity duration alters corticosterone regulation and hence the inflammatory response by comparing the following responses to lipopolysaccharide (LPS; a Gram-negative bacteria component that induces inflammation) of birds caught wild and injected immediately versus those held for 2 or 4 weeks in standard conditions: (1) the magnitude of leukocyte immune gene expression [the cytokines, interleukin 1β and interleukin 6, and Toll-like receptor 4 (TLR4)], (2) the rate of clearance of endotoxin, and (3) the release of corticosterone (CORT) in response to endotoxin (LPS). We predicted that captivity duration would increase baseline CORT and thus suppress gene expression and endotoxin clearance rate. However, our predictions were not supported: TLR4 expression increased with time in captivity irrespective of LPS, and cytokine expression to LPS was stronger the longer birds remained captive. Baseline CORT was not affected by captivity duration, but CORT release post-LPS occurred only in wild birds. Lastly, sparrows held captive for 4 weeks maintained significantly higher levels of circulating endotoxin than other groups, perhaps due to leakage of microbes from the gut, but exogenous LPS did not increase circulating levels over the time scale samples were collected. Altogether, captivity appears to have induced a hyper-inflammatory state in house sparrows, perhaps due to disregulation of glucocorticoids, natural microflora or both.
    Journal of Experimental Biology 08/2011; 214(Pt 15):2579-85. DOI:10.1242/jeb.057216 · 2.90 Impact Factor
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    • "The mechanism leading to sustained arousal in CFS might be hypothesized from stress theory (Figure 2). Infections, which commonly trigger CFS, generally elicit a normal arousal response [45]. Comparable arousal responses can also be elicited by critical life events and perceived chronic difficulties [20], which have been associated with CFS outbreak (Table 1). "
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    ABSTRACT: We present an integrative model of disease mechanisms in the Chronic Fatigue Syndrome (CFS), unifying empirical findings from different research traditions. Based upon the Cognitive activation theory of stress (CATS), we argue that new data on cardiovascular and thermoregulatory regulation indicate a state of permanent arousal responses - sustained arousal - in this condition. We suggest that sustained arousal can originate from different precipitating factors (infections, psychosocial challenges) interacting with predisposing factors (genetic traits, personality) and learned expectancies (classical and operant conditioning). Furthermore, sustained arousal may explain documented alterations by establishing vicious circles within immunology (Th2 (humoral) vs Th1 (cellular) predominance), endocrinology (attenuated HPA axis), skeletal muscle function (attenuated cortical activation, increased oxidative stress) and cognition (impaired memory and information processing). Finally, we propose a causal link between sustained arousal and the experience of fatigue. The model of sustained arousal embraces all main findings concerning CFS disease mechanisms within one theoretical framework.
    Behavioral and Brain Functions 03/2009; 5(1):10. DOI:10.1186/1744-9081-5-10 · 1.97 Impact Factor
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