Abstracts / Brain, Behavior, and Immunity 76 (2019) e1–e43 f
University of Heidelberg, Germany Academic Medical Center Amsterdam (AMC), Netherlands h University of Birmingham, United Kingdom g
Psychological stress induces a beta-adrenergic dependent mobilization of CD8 + T lymphocytes (CTL) into the peripheral blood. Here we identified infection with Cytomegalovirus (CMV) as a major determinant of this mobilization, and characterized the cellular and transcriptional alterations that underlie enhanced responsivity. During acute stress (TSST), CMV-positive individuals (N = 35) demonstrated a 3-fold greater CTL mobilization compared to CMVnegative individuals (N = 48). Enhanced CTL mobilization was entirely confined to cells with an effector-memory phenotype (EMRA), which become markedly enriched in CMV-infected individuals. A beta-adrenergic receptor (beta-AR) dependent mechanism was confirmed by studies showing that stress-induced EMRA mobilization; (1) correlated with catecholamine release; (2) was completely abrogated by the beta-AR antagonist propranolol, and; (3) was reproduced by infusion of the beta-AR agonist isoproterenol. Micro-array analyses demonstrated selective 8-fold up-regulation of the beta2-AR gene (ADRB2) in EMRA as well as CMV-specific CTL. Longitudinal analyses confirmed that CMV-infection de novo induced rapid and lasting ADRB2 up-regulation in CTL, in conjunction with a Th1 T-bet/EOMES transcriptional profile. Subsequent studies in vitro replicated that functional beta2-AR expression increased with progressive CTL differentiation assessed as T-bet/ Th1 expression. The present study identified a novel mechanism through which host–microbe interactions can regulate immune system responses to stress: CMV-infection induced T-bet differentiation accompanied by beta2-AR upregulation, which hereby enriched the CTL compartment with EMRA cells exhibiting an increased adrenergic sensitivity and enhanced mobilization during stress. http://dx.doi.org/10.1016/j.bbi.2018.11.276
Abstract # 3160 Effects of two-week smartphone-based mindfulness training on markers of inflammation: A randomized controlled trial E.K. Lindsay a, A.L. Marsland a, S. Young b, J.M. Smyth c, K.W. Brown d, K. Gray a, C.P. Walsh a, J.D. Creswell e a
University of Pittsburgh, Pittsburgh, PA, United States University of Vermont, United States c Penn State University, United States d Virginia Commonwealth University, United States e Carnegie Mellon University, United States b
Mindfulness interventions, which train people to monitor present-moment experience with a lens of acceptance, are inconsistently associated with reductions in systemic inflammation. Here, we examine the impact of brief mindfulness training on circulating CRP and IL-6, explore treatment response in subgroups at risk for heightened inflammation, and test acceptance training as a mechanism of these effects. 153 stressed community adults were randomly assigned to one of three 14-lesson smartphone-based interventions: (1) training in both monitoring and acceptance (MA), (2) training in monitoring only (MO), or (3) active control training. Dried blood spots collected at pre- and post-intervention were assayed for CRP and IL-6. Contrary to predictions, there were no significant pre- to post-intervention changes in CRP or IL-6 across or between groups. In exploratory subgroup analyses, MA training reduced CRP among both midlife (40–65 years; N = 41) and overweight participants (BMI> = 25; N = 64). Specifically, among midlife participants, MA reduced CRP compared to control (p = .01, d = 0.47) but not MO (p = .57, d = 0.08). Among overweight participants, MA reduced CRP
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compared to both MO (p =.04, d = 0.24) and control (p = .01, d = 0.35). There were no condition differences in these subgroups on changes in IL-6. Overall, two-week mindfulness training did not reduce markers of inflammation in a stressed but otherwise healthy population. Exploratory analyses suggest that this brief mindfulness intervention may reduce CRP in high-risk subgroups, and that acceptance is key for these effects. http://dx.doi.org/10.1016/j.bbi.2018.11.277
Abstract # 3161 Beta-adrenergic receptor mediated inflammation regulation and cardiometabolic risk factors interact to influence cognition in the elderly J. Kohn a, L. Redwine b, N. Guay-Ross a, M.A. Pung a, G. Lyasch a, A. Wilson a, C. Spoon a, C. Pruitt a, S. Hong a, M. Milic a, S. Hong a a University of California – San Diego, Psychiatry, 210 Dickinson St., Bldg A, Rm 402, San Diego, CA 92103, United States b University of South Florida, United States
Inflammation, cardiometabolic risk (CMR) factors, and autonomic imbalance have been independently associated with cognitive declines in aging, but their interactive effect on cognition remains unclear. We quantified the magnitude of their associations with cognitive function and the extent to which links were synergistic. In eighty dementia-free participants (mean = 73.6 years), cognitive function was assessed with the Montreal Cognitive Assessment (MoCA) and CMR was ascertained using principal components analysis on nine serum and blood pressure (BP) measures. Autonomic balance was estimated by delta-BP between 10-min exercise and 1-min cool-down. Beta-adrenergic receptor-mediated inflammation control (BARIC) was quantified by co-incubating immune cells with lipopolysaccharide and beta-agonist for monocyte TNF-alpha expression. Data were analyzed using multivariate linear regression. Of 76 participants who completed MoCA, cognition was impaired in 21 (27.6%; MoCA623) and correlated with age (beta = 0.30, t = 2.56, p = 0.013), but not BMI or gender. Impaired BARIC and higher delta-BP were independently associated with lower MoCA scores (beta = 1.14, t = 2.94, p = 0.005; beta = 0.86, t = 2.32, p = 0.025), adjusted for CMR. For CMR factors, the first component explained 31.5% of total variance, for which higher values reflected hyperglycemia and hyperlipidemia, and significantly predicted lower MoCA scores (beta = 1.20, t = 2.92,p = 0.005). Furthermore, a synergistic effect of BARIC and CMR on MoCA scores was observed (beta = 1.01, t = 3.62, p < 0.001). Sympathoadrenal regulation of inflammation, CMR factors, and autonomic balance exert both independent and synergistic effects on cognitive function in older adults, highlighting a critical role of ANS-immune interactions in aging and cognition. http://dx.doi.org/10.1016/j.bbi.2018.11.278
Abstract # 3162 Salivary cortisol, DHEA-S, and ethnicity in quality of life of cancer caregivers Y. Kim, H. Mitchell, A. Ting, A. Mendez, M. Antoni, C. Carver University of Miami, Coral Gables 33134, United States Stressed caregivers are known to have poorer quality of life (mental and physical health) during the caregiving period. Unknown are prospective longitudinal associations of early caregiving stress with quality of life years later, biological pathways of the associations, and