Overproduction of IL-6, a proinflammatory cytokine, is associated with a spectrum of age-related conditions including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline. To describe the pattern of change in IL-6 over 6 years among older adults undergoing a chronic stressor, this longitudinal community study assessed the relationship between chronic stress and IL-6 production in 119 men and women who were caregiving for a spouse with dementia and 106 noncaregivers, with a mean age at study entry of 70.58 (SD ‫؍‬ 8.03) for the full sample. On entry into this portion of the longitudinal study, 28 of the caregivers' spouses had already died, and an additional 50 of the 119 spouses died during the 6 years of this study. Levels of IL-6 and health behaviors associated with IL-6 were measured across 6 years. Caregivers' average rate of increase in IL-6 was about four times as large as that of noncaregivers. Moreover, the mean annual changes in IL-6 among former caregivers did not differ from that of current caregivers even several years after the death of the impaired spouse. There were no systematic group differences in chronic health problems, medications, or health-relevant behaviors that might have accounted for caregivers' steeper IL-6 slope. These data provide evidence of a key mechanism through which chronic stressors may accelerate risk of a host of age-related diseases by prematurely aging the immune response.

Results point to two potentially orthogonal predisease mechanisms that warrant special attention: cardiovascular activation and sleep dysfunction. Health behavior and cortisol regulation, however, may require more sensitive measures and large sample sizes to discern their roles in loneliness and health.

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These data provide further mechanistic evidence of the sensitivity of wound healing to everyday stressors. Moreover, more frequent and amplified increases in proinflammatory cytokine levels could accelerate a range of age-related diseases. Thus, these data also provide a window on the pathways through which hostile or abrasive relationships affect physiological functioning and health.

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Background The surveillance and effector functions of the immune system are critically dependent on the appropriate distribution of immune cells in the body. An acute or short-term stress response induces a rapid and significant redistribution of immune cells among different body compartments. Stress-induced leukocyte redistribution may be a fundamental survival response that directs leukocyte subpopulations to specific target organs during stress, and significantly enhances the speed, efficacy and regulation of an immune response. Immune responses are generally enhanced in compartments (e.g., skin) that are enriched with leukocytes, and suppressed in compartments that are depleted of leukocytes during/following stress. The experiments described here were designed to elucidate the: 1) Time-course, trajectory, and subpopulation-specificity of stress-induced mobilization and trafficking of blood leukocytes. 2) Individual and combined actions of the principal stress hormones, norepinephrine (NE), epinephrine (EPI), and corticosterone (CORT), in mediating mobilization or trafficking of specific leukocyte subpopulations. 3) Effects of stress/stress hormones on adhesion molecule, L-selectin (CD62L), expression by each subpopulation to assess its adhesion / functional / maturation status. Methods Male Sprague Dawley rats were stressed (short-term restraint, 2–120 min), or adrenalectomized and injected with vehicle (VEH), NE, EPI, CORT, or their combinations, and blood was collected for measurement of hormones and flow cytometric quantification of leukocyte subpopulations. Results Acute stress induced an early increase/mobilization of neutrophils, lymphocytes, helper T cells (Th), cytolytic T cells (CTL), and B cells into the blood, followed by a decrease/trafficking of all cell types out of the blood, except neutrophil numbers that continued to increase. CD62L expression was increased on neutrophils, decreased on Th, CTL, and natural killer (NK) cells, and showed a biphasic decrease on monocytes & B cells, suggesting that CD62L is involved in mediating the redistribution effects of stress. Additionally, we observed significant differences in the direction, magnitude, and subpopulation specificity of the effects of each hormone: NE increased leukocyte numbers, most notably CD62L−/+ neutrophils and CD62L− B cells. EPI increased monocyte and neutrophil numbers, most notably CD62L−/+ neutrophils and CD62L− monocytes, but decreased lymphocyte numbers with CD62L−/+ CTL and CD62L+ B cells being especially sensitive. CORT decreased monocyte, lymphocyte, Th, CTL, and B cell numbers with CD62L− and CD62L+ cells being equally affected. Thus, naïve (CD62L+) vs. memory (CD62L−) T cells, classical (CD62L+) vs. non-classical (CD62L−) monocytes, and similarly distinct functional subsets of other leukocyte populations are differentially mobilized into the blood and trafficked to tissues by stress hormones. Conclusion Stress hormones orchestrate a large-scale redistribution of immune cells in the body. NE and EPI mobilize immune ...

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Objective-Previous research on the physical health consequences of childhood abuse and other adversities has been based on data from young or middle-aged adults. This study addressed the question of whether childhood abuse and other adversities have lasting, detectable consequences for inflammation and cell aging late in life, and whether the effects are large enough to be discernible beyond that of a major chronic stressor, dementia family caregiving.Method-In this community sample of 132 healthy older adults (mean age = 69.70, SD=10.14), including 58 dementia family caregivers and 74 noncaregivers, blood samples were analyzed for interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and telomere length, a measure of cell aging. Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale (CES-D).Results-After controlling for age, caregiving status, gender, body mass index, exercise, and sleep, the presence of multiple childhood adversities was related to both heightened IL-6 (.37 ± .03 vs. .44 ± .03 log10 pg/mL) and shorter telomeres (6.51 ± .17 vs. 5.87 ± .20 Kb), compared to the absence of adversity; the telomere difference could translate into a 7-15 year difference in lifespan. Abuse was associated with heightened IL-6 and TNF-α levels, and, for TNF-α, this relationship was magnified in caregivers compared to controls. Moreover, abuse and caregiving status were significantly and independently associated with higher levels of depressive symptoms.Conclusions-Adverse childhood events are related to continued vulnerability among older adults, enhancing the impact of chronic stressors. Childhood adversities cast a very long shadow. Keywordspsychoneuroimmunology; IL-6; TNF-α; depression; cell aging; trauma Adverse events during childhood have been associated with a higher prevalence of several mental disorders, including DSM-IV-defined mood disorders, disruptive behavior, and substance abuse disorders (1). In fact, simulation data suggested that adversities were associated with 44.6% of all childhood-onset disorders and 25.9% to 32% of adult-onset disorders (1). Adults who experienced abuse or neglect as children appear to have an enhanced emotional sensitivity to stress; they are more likely to develop psychiatric disorders when confronting subsequent stressors than adults who did not have a similarly troubled history (2). Indeed, childhood maltreatment is a particularly potent risk factor for depression in adults, especially when individuals encounter stressful life events (3).In addition to the enhanced emotional stress sensitivity associated with childhood adversity, heightened physiological stress sensitivity has also been documented (3). Alterations in hypothalamic-pituitary-adrenal (HPA) axis and autonomic stress responses have been found in adult survivors of childhood abuse compared to similar individuals without a history of abuse (4,5). Findings from trauma survivors consistent with neuroendocrine stress response sensitization include enhanced glucocorticoi...