Healthy Epstein-Barr virus (EBV) seropositive undergraduates (N = 57) completed a personality inventory, provided blood samples, and were randomly assigned to write or talk about stressful events, or to write about trivial events, during three weekly 20-min sessions, after which they provided a final blood sample. Individuals assigned to the verbal/stressful condition had significantly lower EBV antibody titers (suggesting better cellular immune control over the latent virus) after the intervention than those in the written/stressful group, who had significantly lower values than those in the written/trivial control group. Subjects assigned to the written/stressful condition expressed more negative emotional words than the verbal/stressful and control groups and more positive emotional words than the verbal/stressful group at each time point. The verbal/stressful group expressed more negative emotional words compared with the control group at baseline. Content analysis indicated that the verbal/stressful group achieved the greatest improvements in cognitive change, self-esteem, and adaptive coping strategies.
To address the long-term physiological consequences of chronic stressors, 14 continuing or current family caregivers of Alzheimer's disease (AD) patients, 17 former AD caregivers, and 31 control subjects were compared. Continuing and former caregivers did not differ on depressive symptomatology or perceived stress; both groups were significantly more depressed and stressed than controls. Furthermore, continuing and former caregivers did not differ in the response of NK cells in vitro to recombinant interferon-gamma and recombinant interleukin-2, and both groups had a significantly poorer response to these cytokines than controls. The physiological and psychological consequences of chronic stressors may persist well beyond the cessation of the actual stressor.
The objective of this study was to address the cellular and psychological mechanisms underlying previously observed changes in natural killer (NK) cell cytotoxicity associated with chronic stress. We compared 28 current and former spousal caregivers of patients with Alzheimer's disease (AD) and 29 control subjects. NK cells were enriched (E-NK) using a 4-step procedure that resulted in a cell preparation consisting of 88.2% NK cells. These cells were then incubated with either recombinant interferon-gamma (rIFN-gamma) or recombinant interleukin-2 (rIL-2) for 65 hours. Although an average of over 3 years had elapsed since the death of the patient with AD for the former caregivers, current and former caregivers did not differ in the E-NK cell responses to rIFN-gamma and rIL-2. However, the E-NK cell response for the combined caregiver group was significantly suppressed compared with controls, which is consistent with a previous report from our laboratory. Higher E-NK cell responses to each cytokine were associated with heightened levels of positive emotional and tangible social support, independent of levels of depression. Preliminary data suggest that defects of NK cell function in response to rIFN-gamma and rIL-2 as a consequence of caregiver stress may be independent of non-NK cells. Finally, our data are consistent with other studies regarding the role of social support in immune modulation.
This study investigated the memory T-cell proliferative response to several early and late Epstein-Barr virus (EBV) polypeptides. Blood samples were collected twice, 1 month before a 3-day block of examinations and again on the last day of the exam series. Ss were 25 healthy, EBV seropositive medical students. The proliferative response to 5 of the 6 EBV polypeptides significantly decreased during examinations. In addition, Ss high (above the median) in seeking support, as measured by the COPE, had lower proliferative responses to 3 EBV polypeptides (p17, p52/50, and p85), as well as higher levels of antibody to EBV virus capsid antigen. The data provide further evidence that psychological stress can modulate the cellular immune response to latent EBV.
Based on the theory of psychosomatic inhibition, we hypothesized that subjects who abstained from disclosing emotional material on a laboratory task would have poorer control of latent Epstein-Barr virus (as evidenced by high titers for the viral capsid antigen), and similarly, those subjects with psychometrically derived repressive interpersonal styles would show the highest Epstein-Barr viral capsid antigen titers (EBV-VCA). Eighty first-year undergraduates completed a personality inventory and were asked to write an essay/letter for 30 minutes about a stressful event that had happened in their life. Blood was collected from each subject immediately after writing. Essays were scored for degree of emotional disclosure according to the ratio of emotional-to-total words used. Degree of disclosure was found to be associated with impaired control of latent EBV (high antibody titers to the EBV-VCA) controlling for medication use, recent sleep loss, physical activity, lean body mass, caloric intake, and alcohol and recreational drug use. Further, individual differences in interpersonal style (characterized by emotional suppression) related to this immunologic marker in a similar fashion, and these two factors interacted in determining EBV-VCA titers. That is, Repressors who were either high or low disclosers had high levels of antibody titer to EBV-VCA, whereas only those Sensitizers who did not disclose had high antibody titers to EBV-VCA. In addition to supporting the hypothesis that emotional repression is associated with some aspects of host-virus interaction, the present findings highlight the importance of obtaining behavioral and psychometric assessments in psychoimmunologic investigations of this abstract affective construct (i.e., repression).
We investigated the effects of two behavioral interventions--aerobic exercise and cognitive behavioral stress management (CBSM)--on Epstein-Barr virus viral capsid antigen (EBV-VCA) and human herpesvirus type-6 (HHV-6) antibody modulation in 65 asymptomatic gay men measured at several time points in the 5 weeks preceding and following notification of their human immunodeficiency virus-type 1 (HIV-1) serostatus. After accounting for potential immunomodulatory confounds, we found that HIV-1 seropositive men had higher EBV-VCA antibody titers than those diagnosed as seronegative at every time point during the study; however, no significant differences were found with respect to HHV-6. Among HIV-1 seropositive and seronegative subjects, respectively, those randomized to either behavioral intervention had significant decreases in both EBV-VCA and HHV-6 antibody titers over the course of the intervention as compared with assessment-only controls (of HIV-1 seropositive and seronegative status) whose antibody titers did not significantly change and which remained consistently higher than either serostatus-matched intervention group over subsequent time points, independent of total immunoglobulin G levels and degree of polyclonal B cell activation. In attempting to explain serostatus differences in EBV and HHV-6 values, it was found that HIV-1 seropositive men had significantly lower CD4 cells, CD4:CD8 ratio, and blastogenic response to phytohemagglutinin (PHA), as well as significantly higher CD8 cells at baseline. No significant differences were found between the HIV-1 seropositive and seronegative men with respect to anxiety and depression at baseline. Since the greatest changes in EBV and HHV-6 occurred between baseline and week 10, we correlated changes in immune (CD4, CD8, CD4:CD8 ratio, PHA stimulation) and distress-related markers (state depression and anxiety) with EBV and HHV-6 change scores over this time period. No significant correlations were found between any of these immune- or distress-related variable and the antibody change scores suggesting that the mechanisms by which EBV and HHV-6 antibodies are being modulated by these interventions possibly involve other, yet to be determined, immune, neuroendocrine, and/or psychologic variables.
The relationship of individual differences in repressive coping styles with differences in antibody titer to Epstein-Barr viral capsid antigen (EBV-VCA) were investigated in a normal, healthy college population made up of people previously exposed to EBV. Each of 54 1st-year undergraduates completed a battery of physical-status questions and items pertaining to potential behavioral immunomodulatory confounds, along with the Taylor Manifest Anxiety Scale (T-MAS) and the Marlowe-Crowne Social Desirability Scale (MC-SDS). Ss reporting high and middle levels of anxiety had higher antibody titers to EBV, suggesting poorer immune control over the latent virus, as compared with the low-anxious group. Similarly, high-defensive Ss had higher antibody titers than their low-defensive counterparts, and neither group differed from the middle group.
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