Kate M. Edwards

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.

A general enhancement of autonomic and cortisol responses during social evaluative threat.

Objective: To examine the Social Self Preservation Theory, which predicts that stressors involving social evaluative threat (SET) characteristically activate the hypothalamic-pituitary-adrenal (HPA) axis. The idea that distinct psychosocial factors may underlie specific patterns of neuroendocrine stress responses has been a topic of recurrent debate. Methods: Sixty-one healthy university students (n = 31 females) performed a challenging speech task in one of three conditions that aimed to impose increasing levels of SET: performing the task alone (no social evaluation), with one evaluating observer, or with four evaluating observers. Indices of sympathetic (preejection period) and parasympathetic (heart rate variability) cardiac drive were obtained by impedance- and electrocardiography. Salivary cortisol was used to index HPA activity. Questionnaires assessed affective responses. Results: Affective responses (shame/embarrassment, anxiety, negative affect, and self-esteem), cortisol, heart rate, sympathetic and parasympathetic activation all differentiated evaluative from nonevaluative task conditions (p < .001). The largest effect sizes were observed for cardiac autonomic responses. Physiological reactivity increased in parallel with increasing audience size (p < .001). An increase in cortisol was predicted by sympathetic activation during the task (p < .001), but not by affective responses. Conclusion: It would seem that SET determines the magnitude, rather than the pattern, of physiological activation. This potential to perturb broadly multiple physiological systems may help explain why social stress has been associated with a range of health outcomes. We propose a threshold-activation model as a physiological explanation for why engaging stressors, such as those involving social evaluation or uncontrollability, may seem to induce selectively cortisol release. ECG = electrocardiograph; HPA = hypothalamic-pituitary-adrenal; ICG = impedance cardiograph; PEP = preejection period; RMSSD = root mean square of successive differences; SAM = sympathetic-adrenal-medullary; SET = social evaluative threat; TSST = Trier Social Stress Test.

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.

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.

Racial differences in sleep architecture: the role of ethnic discrimination.

African Americans have been consistently shown to have less deep (slow wave sleep; SWS) and more light (Stages 1 and 2) sleep than Caucasian Americans. This paper explored whether discrimination, a stressor that uniquely impacts certain ethnic groups, contributes to differences in sleep architecture. The sleep of 164 African and Caucasian Americans was examined with laboratory based polysomnography (PSG). Experiences of perceived discrimination (The Scale of Ethnic Experience) and sociodemographic factors were also assessed. After adjusting for age, body mass index (BMI), socioeconomic status (SES) and smoking status, African Americans slept approximately 4.5% more total sleep time (TST) in Stage 2 sleep and 4.7% less TST in SWS than Caucasian Americans (ps<.05). Perceived discrimination was a partial mediator of ethnic differences in sleep architecture. Individuals who reported experiencing more discrimination slept more time in Stage 2 and less time in SWS (ps<.05). Results suggest that the impact of stress related to ethnic group membership plays a part in explaining differences in sleep architecture.

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.

Elevated macrophage migration inhibitory factor (MIF) is associated with depressive symptoms, blunted cortisol reactivity to acute stress, and lowered morning cortisol.

Macrophage Migration Inhibitory Factor (MIF) is a proinflammatory cytokine produced by leukocytes and the secretory cells of the HPA axis. Remarkably, glucocorticoids (GC) induce leukocyte MIF secretion, while MIF renders leukocytes insensitive to the anti-inflammatory effects of glucocorticoids. In light of reported associations between dysphoric states, increased inflammatory activity, and reduced GC sensitivity, the current study investigated the association between MIF, loneliness and depressive symptoms. The study further investigated the relation between plasma MIF and markers of HPA function, i.e., diurnal cortisol and the cortisol response to acute stress. Healthy university undergraduates (N=126; 64 women) were invited to participate if their scores on the Beck Depression Inventory or UCLA loneliness scale were in the upper or lower quintile of their peer group. Plasma MIF and salivary cortisol were measured in response to a public speaking task. Ambulatory diurnal cortisol was assessed for 5 consecutive days. MIF levels were 40% higher in the high-depressive symptoms group compared to the low depressive symptoms group. Elevated MIF was also associated with a smaller cortisol response to acute stress and lower diurnal morning cortisol values. The observed association between HPA function and MIF remained robust after adjustment for depressive symptoms, and demographic, anthropomorphic, and behavioural factors. High levels of depressive symptoms were likewise associated with lower morning cortisol, but this association became non-significant after adjustment for MIF. MIF may be an important neuro-immune mediator linking depressive symptoms with inflammation and HPA dysregulation.

Is obstructive sleep apnea associated with cortisol levels? A systematic review of the research evidence

The pathophysiology of obstructive sleep apnea (OSA) has been associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis; however a relationship between OSA and altered cortisol levels has not been conclusively established. We conducted a systematic review using the PRISMA Guidelines based on comprehensive database searches for 1) studies of OSA patients compared to controls in whom cortisol was measured and 2) studies of OSA patients treated with continuous positive airway pressure (CPAP) in whom cortisol was measured pre and post treatment. Five electronic databases were searched along with the reference lists of retrieved studies. The primary outcomes were 1) differences in cortisol between OSA and control subjects and 2) differences in cortisol pre-post CPAP treatment. Sampling methodology, sample timing and exclusion criteria were evaluated. Fifteen studies met the inclusion criteria. Heterogeneity of studies precluded statistical pooling. One study identified differences in cortisol between OSA patients and controls. Two studies showed statistically significant differences in cortisol levels pre-post CPAP. The majority of studies were limited by assessment of cortisol at a single time point. The available studies do not provide clear evidence that OSA is associated with alterations in cortisol levels or that treatment with CPAP changes cortisol levels. Methodological concerns such as infrequent sampling, failure to match comparison groups on demographic factors known to impact cortisol levels (age, body mass index; BMI), and inconsistent control of variables known to influence HPA function may have limited the results.

The acute stress-induced immunoenhancement hypothesis.

Acute stress, such as a bout of exercise, is accepted to cause an array of immunologic changes. Recently, it has been proposed that acute stress activation of the innate immune system might be harnessed as an adjuvant to enhance immune responses to antigen challenge. This review develops the acute stress-induced immunoenhancement hypothesis and its possible role as a vaccine adjuvant.