Chronic stress and regulation of cellular markers of inflammation in rheumatoid arthritis: Implications for fatigue

Abstract

OBJECTIVES-This study examined whether chronic interpersonal stress is associated with cellular markers of inflammation and regulation of these responses by in vitro doses of glucocorticoids in rheumatoid arthritis (RA) patients. The association between these markers of inflammation and fatigue was also tested.METHODS-Fifty-eight RA patients completed up to 30 daily ratings of the stressfulness of their interpersonal relations. Interleukin-6 (IL-6) production was analyzed in lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cell cultures with and without varying concentrations of the glucocorticoid hydrocortisone. In addition, plasma levels of IL-6 and C-reactive protein (CRP) were analyzed, and subjective ratings of fatigue and pain were obtained on the day of blood sampling, RESULTS-Multilevel modeling showed that higher chronic interpersonal stress was associated with greater stimulated IL-6 production (p < 0.05) as well as greater resistance to hydrocortisone inhibition of IL-6 production (p < 0.05). These relations were not accounted for by demographic factors, body mass index, or steroid medication use. Stimulated production of IL-6, in turn, was associated with greater levels of self-reported fatigue, controlling for pain (p < 0.05). Neither chronic stress ratings nor fatigue symptoms were related to plasma levels of IL-6 or CRP (p's >.05).CONCLUSIONS-Among RA patients, chronic interpersonal stress is associated with greater stimulated cellular production of IL-6 along with impairments in the capacity of glucocorticoids to inhibit this cellular inflammatory response. Moreover, these findings add to a growing body of data that implicate heightened proinflammatory cytokine activity in those at risk for fatigue symptoms.

Markers of Inflammation in Midlife Women with Intimate Partner Violence Histories

“…For example, CRP and IL-6 elevations have been shown to accompany ongoing chronic stressors, such as fear of terrorism 16 and caregiving for a relative with dementia, 17 although again there are exceptions. 18,19 The stress-reactive quality of IL-6 and CRP is consistent with data showing that key biologic stress mediators, glucocorticoids and catecholamines, influence cytokine production. 20 Despite having some shared correlates and despite being biologically linked, IL-6 and CRP sometimes independently predict health risk, 21 and other times they show divergent associations with both health outcomes 22 and stress.…”

“…To our knowledge, this has not been evaluated in the context of remitted chronic stress, but ongoing interpersonal stressors persistent for 1-6 months show positive associations with stimulated IL-6 production from PBMCs or whole blood. 18,26 Third, this article evaluates whether relations between past IPV and biologic measures are accounted for by current symptoms of depression and PTSD. Symptoms of both disorders have been associated with elevations in stimulated IL-6 production and IL-6 and CRP circulating levels in some studies.…”

Neural sensitivity to social rejection is associated with inflammatory responses to social stress

“…Although many stressors can have this effect, animal and human research has shown that social stressors are particularly strong triggers of inflammation (9)(10)(11). Exposure to everyday social stress in humans, for example, is associated with elevated inflammatory activity (12)(13)(14)(15) and with the up-regulated expression of genes that promote inflammation (16). In addition, controlled laboratory studies have shown that acute social stressors-specifically ones that involve social evaluation and the possibility of social rejection-elicit significant increases in proinflammatory cytokines, a key mediator of the inflammatory response (17,18).…”

A new method of treatment of Korsakoff’s (amnestic) psychosis: neurostimulation-correction of the sympathetic nervous system

“…Саморегуляция стресс-реализующей системы осуществляется по прин-ципам обратной связи через влияние адренокор-тикотропного гормона (АКТГ), кортизола на структуры головного мозга [2,3]. Внешняя регу-ляция стресс-лимитирующей системы, способной снизить активность стресс-системы, осуществля-ется через центральное влияние ГАМКергиче-ской, опиоидергической и серотонинергической систем.…”

“…В регуляции стресс-реакции опре-деленное значение играют эндогенные нейропеп-тиды -субстанция Р и мозговой нейротрофиче-ский фактор (BDNF) [5,6]. Комплекс взаимодей-ствия стресс-запускающих и стресс-лимитирую-щих систем, прямых и побочных эффектов фар-макологических средств, патогенетических про-цессов непосредственно болезни способен вы-звать вторичное иммунодефицитное состояние нейрогенного происхождения [2,[7][8][9][10]. В случае отсутствия адаптационных ресурсов вегетативной регуляции координация эндокринной, иммун-ной, сердечно-сосудистой и пищеварительной си-стем осуществляется с помощью центральных ре-гуляторных механизмов посредством гормонов, нейромедиаторов, иммунотаксических агентов [3,11].…”