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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.
In this proposal we argue for an alternative conceptualization of the links
between stress, immunity, and disease that emphasizes stress-induced immune
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. Since inflammation
is an important process in many illnesses (allergic disease, atherosclerosis,
autoimmune disease, and infectious disease), the model has broad implications
for understanding stress-related illness. We propose to test the
model's basic predictions in a study of 25 parents who are experiencing
a severe chronic stressor - having a child with a potentially fatal chronic
illness -- and 25 control parents with a medically healthy child.
All participants will complete a battery of psychosocial instruments and
provide nine saliva samples over the course of a day to assess diurnal
patterns of cortisol secretion. Blood will be collected to assess
whether chronic stress alters the capacity of a synthetic glucocorticoid
(dexamethasone) to suppress the in vitro production of pro-inflammatory
cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha.
Four questions will be addressed: How does chronic psychological
stress influence diurnal patterns of cortisol secretion? How does
chronic stress influence the immune systems' response to signals that terminate
the inflammatory cascade? To what extent do psychological responses
to chronic stress influence biological processes? To what extent
do psychosocial vulnerability markers, such as cynical |
(MS
WORD VERSION)
