Victoria E. Burns

Acute stress exposure prior to influenza vaccination enhances antibody response in women

Animal studies have shown that an acute stressor in close temporal proximity to immune challenge can enhance the response to delayed-type hypersensitivity and antibody response to vaccination. The current study examined the effects of acute exercise or mental stress prior to influenza vaccination on the subsequent antibody response to each of the three viral strains. Sixty young healthy adults (31 men, 29 women) were randomly allocated to one of three task conditions: dynamic exercise, mental stress, or control. After an initial baseline, participants completed their allocated 45 min task and then received the influenza vaccine. Plasma cortisol and interleukin-6 were determined at the end of baseline, after the task, and after 60 min recovery. Antibody titres were measured pre-vaccination and at 4 weeks and 20 weeks post-vaccination follow-ups. For the A/Panama strain, women in both the exercise and mental stress conditions showed higher antibody titres at both 4 and 20 weeks than those in the control condition, while men responded similarly in all conditions. Interleukin-6 at +60 min recovery was found to be a significant predictor of subsequent A/Panama antibody response in women. In line with animal research, the current study provides preliminary evidence that acute stress can enhance the antibody response to vaccination in humans.

Eccentric exercise as an adjuvant to influenza vaccination in humans.

The immune response to vaccination in animals can be enhanced by exposure to acute stress at the time of vaccination. The efficacy of this adjuvant strategy for vaccination in humans requires investigation. The current study employed a randomised controlled trial design to examine the effects of eccentric exercise prior to influenza vaccination on the antibody and cell-mediated responses. Sixty young healthy adults (29 men, 31 women) performed eccentric contractions of the deltoid and biceps brachii muscles of the non-dominant arm (exercise group) or rested quietly (control group), and were vaccinated 6h later in the non-dominant arm. Change in arm circumference and pain were measured to assess the physiological response to exercise. Antibody titres were measured pre-vaccination and at 6- and 20-week follow-ups. Interferon-gamma in response to in vitro stimulation by the whole vaccine, an index of the cell-mediated response, was measured 8 weeks post-vaccination. Interferon-gamma responses were enhanced by exercise in men, whereas antibody titres were enhanced by eccentric exercise in women but not in men. Men showed greater increase in arm circumference after eccentric exercise than women but there was no difference in reported pain. The interferon-gamma response was positively associated with the percentage increase in arm circumference among the exercise group. Eccentric exercise exerted differential effects on the response to vaccination in men and women, with enhancement of the antibody response in women, but enhancement of the cell-mediated response in men. Eccentric exercise of the muscle at the site of vaccine administration should be explored further as a possible behavioural adjuvant to vaccination.

Mobilization of γδ T lymphocytes in response to psychological stress, exercise, and β-agonist infusion

The mobilization of cytotoxic lymphocytes, such Natural Killer (NK) cells and CD8(+) T cells, during stress and exercise is well documented in humans. However, humans have another cytotoxic lymphocyte subset that has not been studied in this context: the Gamma Delta (gammadelta) T lymphocyte. These cells play key roles in immune processes including the elimination of bacterial infection, wound repair and delayed-type hypersensitivity reactions. The current study investigated the effects of stress, exercise, and beta-agonist infusion on the mobilization of gammadelta T lymphocytes. Three separate studies compared lymphocytosis in response to an acute speech stress task (n=29), high (85%W(max)) and low (35%W(max)) intensity concentric exercise (n=11), and isoproterenol infusion at 20 and 40 ng/kg/min (n=12). Flow cytometric analysis was used to examine lymphocyte subsets. gammadelta T lymphocytes were mobilized in response to all three tasks in a dose-dependent manner; the extent of mobilization during the speech task correlated with concomitant cardiac activation, and was greater during higher intensity exercise and increased dose of beta-agonist infusion. The mobilization of gammadelta T lymphocytes was greater (in terms of % change from baseline) than that of CD8(+) T lymphocytes and less than NK cells. This study is the first to demonstrate that gammadelta T cells are stress-responsive lymphocytes which are mobilized during psychological stress, exercise, and beta-agonist infusion. The mobilization of these versatile cytotoxic cells may provide protection in the context of situations in which antigen exposure is more likely to occur.

Antibody response to vaccination and psychosocial stress in humans:relationships and mechanisms.

The purpose of this review is to determine the effects of psychosocial stress on antibody response to vaccination in humans, consider possible mechanisms, and identify agenda for future research. Studies of the association between stress and vaccination response in humans were reviewed. There is evidence of a negative association between stress and antibody response to vaccination, which is most apparent with thymus-dependent vaccines and when measured at extended times after vaccination. Preliminary findings implicate the hypothalamic-pituitary-adrenal axis and sympathetic nervous system as potential mechanisms, although a role for unhealthy behaviours cannot be discounted at this stage. Results to date are sufficiently indicative to direct future research to untangling their theoretical ramifications, as well as realising their clinical implications.

Meningococcal A vaccination response is enhanced by acute stress in men.

Objective: To determine if acute stress experienced at the time of antigenic challenge augments the subsequent immune response. Methods: Sixty healthy young adults were randomized to exercise (n = 20), mental stress (n = 20) or control (n = 20) before meningococcal A+C vaccination. Antibody concentration was measured by microsphere-based antibody quantification assay at prevaccination, 4 and 20 weeks post vaccination. Results: Meningococcal serogroup A antibody responses were enhanced by exercise and mental stress in men but not women (F(2,51) = 4.00, p = .02, &eegr;2 = 0.135). Conclusions: Stress-induced immune enhancement has now been demonstrated in the antibody response to thymus-independent as well as thymus-dependent vaccines. These findings indicate that this effect is not specific to T-cell involvement. IgG = immunoglobulin G.

Stress, coping, and hepatitis B antibody status

Objective The present study investigated the association between exposure to stressful life events, coping style, and antibody status after hepatitis B vaccination. Methods Two hundred sixty medical school undergraduates, who had received the three-dose hepatitis B vaccine before recruitment to this study, completed questionnaires measuring exposure to stressful life events during the past year, customary coping strategies, and health behaviors. Antibodies against hepatitis B surface antigen were determined; levels <100 mIU/ml were deemed inadequate. Results Two participant cohorts were identified: those vaccinated within the last year and those vaccinated earlier. In the early vaccination cohort, participants with greater-than-average stress exposures had a more than two-fold increased risk of having an inadequate antibody titer. Coping by accepting the reality of stressful situations proved protective, whereas coping by substance use increased the risk of having an inadequate antibody count in this cohort. These associations remained significant after adjustment for possible mediators. Furthermore, the effects of stress and coping were largely independent of one another. Neither stress nor coping was significantly associated with antibody status in the recently vaccinated cohort. Conclusions The present study confirms that the immune system is sensitive to variations in psychological factors. Stressful life events and coping strategy seem to have a continuing impact on hepatitis B antibody status.

The association between life events, social support and antibody status following thymus-dependent and thymus-independent vaccinations in healthy young adults

This study determined whether stressful life events and social support were related to antibody status following both thymus-dependent and thymus-independent vaccinations. Life events in the previous year and customary social support were measured in 57 healthy students at baseline. Antibody status was also assessed at baseline and at five weeks and five months following vaccination with the trivalent influenza vaccine and the meningococcal A+C polysaccharide vaccine. Taking into account baseline antibody titre, high life events scores prior to vaccination were associated with lower responses to the B/Shangdong influenza strain at both five weeks and five months and meningococcal C at five weeks. Life event scores were not associated with response to the other two influenza viral strains nor response to meningococcal A. Those with high social support scores had stronger 5-week and 5-month antibody responses to the A/Panama influenza strain, but not to any of the other strains. These associations could not be accounted for by demographic or health behaviour factors, and also emerged from analyses comparing those who exhibited a fourfold increase in antibody titre from baseline with those who did not. Life events and social support were related to antibody status following influenza vaccination in distinctive ways that may be partly determined by vaccine novelty and prior naturalistic exposure. Life events also predicted poor antibody response to meningococcal C polysaccharide vaccination after previous meningococcal C conjugate vaccination. Neither psychosocial factor was associated with response to primary meningococcal A polysaccharide vaccination.

Life events, perceived stress and antibody response to influenza vaccination in young, healthy adults.

OBJECTIVES Chronic stress has been associated with impaired response to influenza vaccination in the elderly. This study investigated whether mild, intermittent stress experienced by young, healthy adults has a similar effect. METHODS Antibody and psychological status were determined prevaccination and 5 weeks and 5 months later; a fourfold increase in antibody to at least one viral strain was considered protective. RESULTS At 5 months, unprotected participants reported significantly more life events and tended to report more perceived stress than those who were protected. CONCLUSIONS Psychological stress is detrimental to long-term maintenance of antibody levels following vaccination in young, healthy adults.

Sex differences in the interleukin-6 response to acute psychological stress.

Interleukin-6 (IL-6), an immune regulator that helps coordinate the inflammatory response, may mediate inflammatory disease exacerbation associated with stress. Twenty men and twenty women completed a single session, comprising baseline (20 min), mental arithmetic task (8 min), and recovery (60 min). Blood samples, taken at baseline, immediately after the task, and at +30 and +60 min recovery were analysed for plasma IL-6. Overall, IL-6 increased linearly from baseline to +60 min recovery, and a sex difference was found in the IL-6 response, with men peaking earlier than women. These findings confirm a small delayed IL-6 increase after acute laboratory stress, and reveal sex differences in the profile of the IL-6 response.

Stress and exercise : Getting the balance right for aging immunity

Age-related immunological and endocrinological changes may have implications for resilience to stress in older adults. We hypothesize that the combination of adrenopause and immunosenescence may leave this population particularly vulnerable to the negative effects of stress on immunity. We propose that exercise may be an effective intervention to limit the impact of stress on immunity in chronically stressed older populations.