investigator?s abstract): Psychological stress has been linked with a broad array of adverse health outcomes. A central assumption of the models that guide this work is that stress accomplishes this by suppressing the immune response in a way that leaves the host vulnerable to disease. While these models account for some important outcomes, they do not parsimoniously explain how stress might influence illnesses whose central feature is excessive immunologic activation. This pilot study proposes an alternative conceptualization of the links between stress, immunity, and disease that emphasizes stress-induced dysregulation. Its basic premise is that by activating the hypothalamic-pituitary-adrenal (HPA) axis, psychological stress renders the immune system unresponsive to signals that terminate the inflammatory cascade thus influencing the outcome of disease states where inflammation is an important mediator of the pathogenic process. In order to test this new conceptualization a model system employing 25 patients who are experiencing a severe chronic stressor --- having a child with a potentially fatal chronic illness-and 25 control patients with a medically healthy child. All participants will complete a battery of psychosocial instruments and provide multiple salivary samples to assess diurnal patterns of cortisol secretion. Blood samples will also be obtained to assess whether chronic stress alters the capacity of a synthetic glucocorticoid to suppress the in vitro production of the proinflammatory cytokines, interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha. These experiments will address the questions: 1) How does chronic psychological stress influence diurnal patterns of cortisol secretion; 2) How does chronic stress influence the immune system?s response to signals that terminate the inflammatory cascade; 3) To what extent do psychological responses to chronic stress influence biological processes and 4) To what extent do psychosocial vulnerability markers additionally influence the impact of chronic stress on biological processes' Data from this pilot study will form the basis for submission of a larger application examining psychological stress, HPA function and inflammation.
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