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This review focuses on human psychoneuroimmunology studies published in the past decade. Issues discussed include the routes through which psychological factors influence immune function, how a stressor's duration may influence the changes observed, individual difference variables, the ability of interventions to modulate immune function, and the health consequences of psychosocially mediated immune dysregulation. The importance of negative affect and supportive personal relationships are highlighted. Recent data suggest that immune dysregulation may be one core mechanism for a spectrum of conditions associated with aging, including cardiovascular disease, osteoporosis, arthritis, Type 2 diabetes, certain cancers, and frailty and functional decline; production of proinflammatory cytokines that influence these and other conditions can be stimulated directly by negative emotions and indirectly by prolonged infection.

Background: A number of studies have shown that the chronic stress of caring for persons with dementia can have significant immunological consequences as demonstrated by the down-regulation/dysregulation of the cellular immune response., Methods: Utilizing flow cytometry to measure the percentages and absolute numbers of CD-4(+) and CD-8(+) T lymphocytes producing the cytokines indicative of Th-1, Tc1 and Th-2, and Tc2 cells, we compared spousal caregivers and control subjects. The expression of interleukin-2 (IL-2), interferon gamma (IFN-gamma), and interleukin-10 (IL-10) in the cytoplasm of CD-4(+) and CD-8(+) lymphocytes was assessed., Results: Neither stress nor age was significantly related to the percentage or number of IFNgamma(+)/CD-8(+), IL-2(+)/CD-8(+) cells, or IFNgamma(+), IL-2(+), CD-4(+) cells. However, the percentage of IL-10(+) cells was higher in lymphocytes obtained from caregivers than control subjects. In addition, the significant interaction between stress and aging for IL-10(+)/CD-4(+) and IL-10(+)/CD-8(+) cells demonstrated that the difference between caregivers and control subjects was age dependent; the difference between caregivers and control subjects was substantially larger in younger individuals than in older individuals., Conclusions: The data are consistent with previous reports on acute stress and suggest that there may also be a shift from a Th-1 to a Th-2 response associated with a chronic stressor such as caregiving. This shift could have implications for an individual's responses to pathogens.

It is now accepted that there are complex interactions among the central nervous system, the endocrine system, and the immune system. Although the mechanisms of this bi-directional communication is not yet fully understood, studies in the field of psychoneuroimmunology (PNI) have shown that stress, through the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal medullary (SAM) axes, can induce modulation of the immune system. In this review, we discuss human studies and animal models, which focus on psychological stress and its effects on the immune defense against infectious agents, emphasizing the implications of these effects on health.

Ninety newlywed couples (mean age = 25), selected on the basis of extremely stringent mental and physical health criteria, were admitted to a hospital research unit for 24 hours to provide a detailed assessment of conflict-resolution behaviors and changes in autonomic, endocrine, and immune function. Among these newlyweds, negative or hostile behaviors during marital conflict (coded from videotaped interactions) were associated with increased levels of epinephrine, norepinephrine, growth hormone, and ACTH as well as greater immunological change over the subsequent 24 hours. Wives demonstrated greater and more persistent physiological changes related to marital conflict than husbands. To assess the generalizability of these physiological changes, a similar laboratory paradigm was used with 31 older couples (mean age = 67) who had been married an average of 42 years. Consistent with the data from newlyweds, both endocrinological and immunological data showed significant relationships to negative behavior during marital conflict in these older couples. These findings suggest that abrasive marital interactions have important endocrinological and immunological correlates.

We examined the effects of brief psychological stressors on cardiovascular, neuroendocrine, and cellular immune response in 22 older women to investigate the common effects of stress across systems. Results revealed that psychological stressors heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected the cellular immune response (ps < 0.05). In a replication and extension, 27 women caring for a spouse with a progressive dementia (high chronic stress) and 37 controls category matched for age and family income (low chronic stress) performed the 12-min laboratory stressor. Measures were taken before (low acute stress) and immediately following (high acute stress) exposure to the laboratory stressors as well as 30 min after termination of the stressor (recovery period). Acute stress again heightened cardiac sympathetic activation, elevated plasma catecholamine concentrations, and affected cellular immune responses (ps < 0.05), whereas chronic stress was associated with higher reports of negative affect, enhanced cardiac sympathetic activation, elevated blood pressure and plasma levels of ACTH, and diminished production of interleukin-1 beta (ps < 0.05). Correlational analyses in both studies further suggested that individuals who showed the greatest stress-related changes in HPA activation also exhibited the greatest diminution in cellular immune response.

We compared virus-specific antibody and T-cell responses to influenza virus vaccination in 32 caregivers of Alzheimer's disease (AD) patients and matched control subjects. Caregivers showed a poorer antibody response and virus-specific T-cell response following vaccination compared to the control subjects as measured by fourfold increases in antibody titers to the vaccine and lower levels of virus-induced IL-2 levels in vitro. We performed a second study in which forty-eight medical students were inoculated with a series of three injections of the hepatitis-B (HEP-B) vaccine to coincide with the third day of three, three-day examination blocks. Twelve of the 48 medical students seroconverted after the first injection; these students were characterized by falling into the lower stressed/lower anxiety group of students. Students who reported greater social support and lower anxiety and stress demonstrated a higher antibody response to the vaccine and a more vigorous T-cell response to HEP-B surface antigen at the end of the third examination experience. The differences in antibody and T-cell responses to HEP-B and influenza virus vaccinations provide a demonstration of how stress may be able to alter both the cellular and humoral immune responses to vaccines and novel pathogens in both younger and older adults.

This paper summarizes important methodological issues that are particularly relevant for behavioral immunology research with humans. The assessment of such salient parameters as nutrition, drug/alcohol use, physical activity, and health are discussed. In addition, a number of logistical issues are addressed.

Background: It has been demonstrated that growth hormone (GH) is synthesized and secreted by human peripheral mononuclear cells (PBMC), and the expression of GH mRNA can be found throughout the human immune system.Methods: We studied a population of female caregivers of patients with Alzheimer's dementia (AD) who suffered from the stress of caring for these patients. We utilized quantitative RT-PCR to determine GH mRNA levels in T- and B-cell populations from PBMC. Subjects were nine caregivers of AD patients and nine age- and sex-matched controls.Results: In the control group we found a threefold greater GH mRNA expression in B cells than in T cells. This finding was consistent with our previous in situ hybridization observation, suggesting GH mRNA in predominately B-cell areas of immune organs in humans. We also found that the expression of GH mRNA from total peripheral blood mononuclear cells and B cells in caregivers was 50% and 60% respectively less than that in the control group.Conclusions: Because the B-cell population is the source of antibody production, our findings suggest that the decrease in B-cell GH mRNA may contribute to the poor immune response to influenza virus vaccination that has been reported previously in chronically stressed caregivers. [ABSTRACT FROM AUTHOR]

Stress-induced immune dysregulation during pregnancy may contribute to adverse birth outcomes. As a robust indicator of cellular immune competence, we examined EBV reactivation in association with gestational age, race, racial discrimination, and preterm birth among 56 women. We assessed psychosocial factors and serum EBV capsid antigen antibody titers at each trimester and ∼5weeks postpartum. African–Americans (n =38) and Whites (n =18) did not differ in age, income, parity, or BMI (ps⩾.51). EBV reactivation was lower in 3rd versus 1st trimester (p =.002). At every timepoint, African–Americans showed greater EBV reactivation than Whites (ps<.001). This effect was strongest among African–Americans reporting greater racial discrimination [p =.03(1st), .04(2nd), .12(3rd), .06(postpartum)]. Associations of race and discrimination with EBV reactivation were not accounted for by perceived stress, depressive symptoms, anxiety, or health behaviors. In the full sample, controlling for race, for every 2-fold increase in EBV antibody titers, the odds of preterm birth were 3.4 times higher (95%CI=1.4, 11.9, p =.02). In African–Americans, the odds of preterm birth were 4.0 times higher for each 2-fold increase in antibody titers (95%CI=1.3, 23.6), p =.01]. The ability of the cellular immune response to suppress latent EBV is enhanced in late compared to early gestation. Compared to Whites, African–American women show impaired cellular immune competence across pregnancy and postpartum, particularly those reporting greater racial discrimination. EBV reactivation may be associated with increased odds of preterm birth, particularly among African–Americans. [ABSTRACT FROM AUTHOR]

Focuses on the role of stress in modulating cellular immune function. Link between the central nervous system and the immune system through a network of bidirectional signals; Disruption of the homeostasis of the network by stress; Implications of the downregulation of the cellular immune response on health.