The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions.

To determine whether a chronic stressor (caregiving for a spouse with a progressive dementia) is associated with an impaired immune response to influenza virus vaccination, we compared 32 caregivers' vaccine responses with those of 32 sex-, age-, and socioeconomically matched control subjects. Caregivers showed a poorer antibody response following vaccination relative to control subjects as assessed by two independent methods, ELISA and hemagglutination inhibition. Caregivers also had lower levels of in vitro virus-specific-induced interleukin 2 levels and interleukin 1beta; interleukin 6 did not differ between groups. These data demonstrate that down-regulation of the immune response to influenza virus vaccination is associated with a chronic stressor in the elderly. These results could have implications for vulnerability to infection among older adults.

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Chronic stress alters the immune response to influenza virus vaccine in older adults

Objective: Although psychological modulation of immune function is now a well-established phenomenon, much of the relevant literature has been published within the last decade. This article speculates on future directions for psychoneuroimmunology research, after reviewing the history of the field. Methods: This review focuses on human psychoneuroimmunology studies published since 1939, particularly those that have appeared in Psychosomatic Medicine. Studies were clustered according to key themes, including stressor duration and characteristics (laboratory stressors, time-limited naturalistic stressors, or chronic stress), as well as the influences of psychopathology, personality, and interpersonal relationships; the responsiveness of the immune system to behavioral interventions is also addressed. Additionally, we describe trends in populations studied and the changing nature of immunological assessments. The final section focuses on health outcomes and future directions for the field. Results: There are now sufficient data to conclude that immune modulation by psychosocial stressors or interventions can lead to actual health changes, with the strongest direct evidence to date in infectious disease and wound healing. Furthermore, recent medical literature has highlighted a spectrum of diseases whose onset and course may be influenced by proinflammatory cytokines, from cardiovascular disease to frailty and functional decline; proinflammatory cytokine production can be directly stimulated by negative emotions and stressful experiences and indirectly stimulated by chronic or recurring infections. Accordingly, distress-related immune dysregulation may be one core mechanism behind a diverse set of health risks associated with negative emotions. Conclusions: We suggest that psychoneuroimmunology may have broad implications for the basic biological sciences and medicine. CRP C-reactive protein; DTH delayed-type hypersensitivity; EBV Epstein-Barr virus; HLA human leukocyte antigen; HSV herpes simplex virus; Ig immunoglobulin; IL interleukin; NK natural killer; PHA phytohemagglutinin; PNI psychoneuroimmunology; PTSD posttraumatic stress disorder.

/pdf/psychoneuroimmunology-and-psychosomatic-medicine-back-to-the-3vzx88lcxx.pdf

Psychoneuroimmunology and psychosomatic medicine: back to the future.

The acquisition and extinction of the conditioned suppression or enhancement of one or another parameter of antigen-specific and nonspecific defense system responses have been documented in different species under a variety of experimental conditions. Similarly, stressful stimulation influences antigen-specific as well as nonspecific reactions. Moreover, both conditioning and stressful stimulation exert biologically meaningful effects in the sense that they can alter the development and/or progression of what are presumed to be immunologically mediated pathophysiologic processes. These are highly reproducible phenomena that illustrate a functional relationship between the brain and the immune system. However, the extent to which one can generalize from one stressor to another or from one parameter of immunologic reactivity to another is limited. Few generalizations are possible because the direction and/or magnitude of the effects of conditioning and "stress" in modulating immune responses clearly depend on the quality and quantity of the behavioral interventions, the quality and quantity of antigenic stimulation, the temporal relationship between behavioral and antigenic stimulation, the nature of the immune response and the immune compartment in which it is measured, the time of sampling, a variety of host factors (e.g. species, strain, age, sex), and interactions among these several variables. It seems reasonable to assume that the immunologic effects of behaviorally induced neural and endocrine responses depend on (interact with) the concurrent immunologic events upon which they are superimposed. Conversely, the efficacy of immunologic defense mechanisms seems to depend on the neuroendocrine environment on which they are superimposed. We seek to determine when and what immunologic (or neuroendocrine) responses could be affected by what neuroendocrine (or immunologic) circumstances. We therefore need studies that provide a parametric analysis of the stimulus conditions, the neuroendocrine and/or immunologic state upon which they are superimposed, and the responses that are being sampled. The neural or neuroendocrine pathways involved in the behavioral alteration of immune responses are not yet known. Both conditioning and stressor-induced effects have been hypothesized to result from the action of adrenocortical steroids, opioids, and catecholamines, among others. Indeed, all of these have been implicated in the mediation of some immunologic effects observed under some experimental conditions. We assume that different conditioning and stressful environmental circumstances induce different constellations of neuroendocrine responses that constitute the milieu within which ongoing immunologic reactions and the response to immunologic signals occur.(ABSTRACT TRUNCATED AT 400 WORDS)

http://psych415.class.uic.edu/Readings/Ader,%20Conditioning%20-%20immunology,%20AnnRevPsy,%201993.pdf

Psychoneuroimmunology: Conditioning and Stress

The mammalian response to stress involves the release of soluble products from the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Cells of the immune system respond to many of the hormones, neurotransmitters, and neuropeptides through specific receptors. The function of the immune system is critical in the mammalian response to infectious disease. A growing body of evidence identifies stress as a cofactor in infectious disease susceptibility and outcomes. It has been suggested that effects of stress on the immune system may mediate the relationship between stress and infectious disease. This article reviews recent psychoneuroimmunology literature exploring the effects of stress on the pathogenesis of, and immune response to, infectious disease in mammals.

Psychoneuroimmunology: stress effects on pathogenesis and immunity during infection.

The stress of physical restraint has been shown to modulate the cellular immune response during a viral infection. We have studied the effects of stress on the humoral immune response during infection by influenza virus. Restraint stress altered the kinetics of the antibody response; seroconversion in the IgG and IgA isotypes was delayed in virus-infected C57BL/6 mice subjected to repeated cycles of physical restraint. However, the magnitude and isotype of the mature antibody response were unaffected during the plateau phase; no significant differences were observed between restrained/infected and nonrestrained/infected mice. Thus, the time during infection at which the antibody response was measured was a significant variable in the study of stress-induced alterations of the host's response to a replicating viral antigen. While restraint stress did not significantly affect the magnitude or class of the humoral response, it did alter the kinetics of response.

R. Pagniano

Papers

The effect of restraint stress on the kinetics, magnitude, and isotype of the humoral immune response to influenza virus infection.