Robert J. Benschop

Cardiovascular and Immune Responses to Acute Psychological Stress in Young and Old Women: A Meta-Analysis

Objective To describe the relationships between cardiovascular and natural killer (NK) cell number changes on acute psychological stress in women. Method Data from eight different studies were analyzed. A total of 128 healthy female subjects, 85 younger (18-45 years) and 43 older (49-87 years), had been subjected to a speech stressor (N = 80) or a mental effort stressor (N = 48), mental arithmetic, or the Stroop test. Correlations between changes in NK cell numbers, systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) were computed. Meta-analysis programs were used to study correlations across studies and to examine whether correlations differed with stressors or age. Results In all studies, significant increases over baseline were observed for each variable. Across studies, the mean weighted r between changes in HR, DBP, and SBP was medium (rw = .25) to large (rw = .64). A medium to large average correlation between HR and NK changes (rw = .37) was observed, whereas average correlations of changes in NK cell numbers with blood pressure changes were small to medium (rw <or=to .23). Correlations between changes in NK cell numbers and cardiovascular variables were homogeneous across studies, whereas mutual correlations between cardiovascular variables were heterogeneous. One moderator variable showed itself: correlations between HR and DBP reactions were larger in studies with older than younger subjects. Conclusion NK cell changes and HR responses induced by acute stress in women are regulated, to some extent, by the same mechanisms. Neither the type of stressor nor age seem to be very important when considering correlations between NK cell and cardiovascular changes. This study integrates information about NK cell and cardiovascular responses in women that can be used as reference material in future studies.

The effects of β‐adrenoceptor stimulation on adhesion of human natural killer cells to cultured endothelium

1 The circulation of natural killer (NK) cells in vivo is influenced by physical exercise, mental stress, and infusion of β‐adrenoceptor agonists. We have previously presented in vitro data, showing that β2‐adrenoceptor agonists induce detachment of NK cells from endothelial cells (EC), supporting the hypothesis that NK cells can be recruited from the marginating pool in blood vessels. 2 Because NK cells as well as EC express β2‐adrenoceptors, the present study was conducted to investigate whether stimulation of the β‐adrenoceptors on NK cells, EC or both cell types is required to induce detachment from EC. 3 Cells were pretreated (15min) with a selective β2‐adrenoceptor antagonist, GR81706, at various concentrations. The duration of β‐adrenoceptor blockade was tested by determining the adenosine 3′,5′‐cyclic monophosphate (cyclic AMP) production induced by terbutaline (a β2‐adrenoceptor specific agonist). This receptor‐mediated response was effectively inhibited for at least 4 h, whereas the cyclic AMP production in response to forskolin (a direct activator of adenylate‐cyclase) was not affected. 4 Functional adhesion assays were then performed to determine the role of β‐adrenoceptors on the different cell types involved (NK and EC) in catecholamine‐induced detachment. Peripheral blood mononuclear cells were allowed to adhere for 1 h to monolayers of unstimulated EC in the presence or absence of cyclic AMP inducing agents, and the percentage of NK cells in the adhering lymphocyte fraction was determined by flow cytometry. 5 Both adrenaline (10−5 m) and forskolin (10−5 m) caused detachment of NK cells from EC. After blockade of the β2‐adrenoceptors on NK cells by pretreatment with GR81706 (10−6 m), the effect of adrenaline on NK cells adhesion was pretented; after blockade of the β2‐adrenoceptors on EC, NK cell adhesion was still significantly reduced by adrenaline. In all cases, forskolin caused detachment of NK cells. 6 To establish further that stimulation of β‐adrenoceptors on NK cells is sufficient to cause detachment, we showed that adrenaline also reduced adhesion of NK cells to monolayers of Chinese hamster ovary cells, which do not express β‐adrenoceptors. 7 Together, these results show that stimulation of β2‐adrenoceptors on NK cells negatively influences their capacity to adhere to EC, and that β2‐adrenoceptors on EC play a negligible role in this phenomenon.

Relationships Between Cardiovascular and Immunological Changes in an Experimental Stress Model

To investigate the relationships between cardiovascular variables (SBP, DBP, and HR) and circulating natural killer (NK) cell numbers, 70 male volunteers were subjected to a rest condition (N = 30) or a stressful laboratory task (N = 40). At baseline, no significant relationships could be demonstrated between the number of NK cells and the cardiovascular variables. Analysis of covariance showed that the stressor induced increases in the number of NK cells, SBP, DBP, and HR. Changes in Nk cell numbers were highly correlated to changes in cardiovascular variables in both the task and the no-task group. These results indicate that there is no relationship between the number of circulating NK cells and cardiovascular levels per se, but that changes in these variables, either stress-induced or under rest conditions, are regulated by a common mechanism.

Psychobiological factors related to human natural killer cell activity and hormonal modulation of NK cells in vitro

The present report investigated whether percentages of circulating natural killer (NK) cells and NK cell activity (NKCA) are associated with psychological variables. Subjects (n = 95) were selected, based on a combination of low or high scores on questionnaires on daily hassles and self-reported symptoms, to create four extreme groups. NK cell percentages were different between two of the four groups, only when the analysis was not controlled for gender, life style and endocrine parameters. No evidence was found for a relationship between group membership and NKCA. NKCA, however, was found to differ between men and women and to be associated with percentages of NK cells and intracellular levels of cAMP. Furthermore, the hypothesis was tested, that hormone-induced changes in NKCA in vitro are dependent on the individuals current stress profile. To investigate this issue, NKCA was measured after cells had been incubated with hydrocortisone (10(-6) or 10(-7) M) or the beta-adrenergic agonist isoprenaline (10(-5) or 10(-7) M) in vitro. Changes in NKCA were found to be related to plasma adrenaline levels, but no evidence was found for involvement of psychological variables. It is concluded that, in the current setting, there is no association between the combination of scores on the two psychological questionnaires, and NKCA or hormone-induced changes therein.

Immunologic, endocrine and psychological influences on cortisol-induced immunoglobulin synthesis in vitro

In the present study, the relationship between psychological variables and hydrocortisone (HC)-induced immunoglobulin (Ig) production in vitro was investigated. Ninety-five human volunteers were selected based on their extreme (low or high) scores on a daily hassles and a symptoms questionnaire. Four groups were composed: (1) few hassles, few symptoms; (2) many hassles, few symptoms; (3) few hassles, many symptoms; and (4) many hassles, many symptoms. Incubating peripheral blood mononuclear cells (PBMC) for 2 weeks with HC (concentrations ranging from 10(-8) to 10(-6) M), resulted in a concentration-dependent rise in IgM and IgG secretion. In vitro IgM as well as IgG secretion were found to be related to plasma Ig levels. Plasma cortisol levels were positively associated with HC-induced IgG secretion. Furthermore, Ig secretion was found to depend on psychological profile, indicating a differential sensitivity of PBMC to HC for the four groups.