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Impact of chronic and acute academic stress on lymphocyte subsets and monocyte function

• Viktoriya Maydych,
• Maren Claus,
• Nicole Dychus,
• Melanie Ebel,
• Jürgen Damaschke,
• Stefan Diestel,
• Oliver T. Wolf,
• Thomas Kleinsorge,
• Carsten Watzl

ten

• Published: November 16, 2017
• https://doi.org/10.1371/journal.pone.0188108

Figures

Abstract

This report investigated the effects of a temporally confined naturalistic stressor (academic stress) on allowed functions. Furthermore, moderating influences of a number of psychological variables were assessed. Five blood samples were obtained from 20 students during an observation period of 8 weeks, starting iv.5 weeks before an exam period up to one week following the last exam. The assay of 45 immune parameters revealed several time-dependent changes attributable to examination stress. We observed a reduction in the absolute numbers of natural killer (NK) cells and monocytes in peripheral blood and a shift towards more young and naïve cells within NK and T jail cell populations. In addition, IL-half dozen and TNF-α production by LPS-stimulated monocytes was increased. Psychological variables were grouped by means of factor analyses into two factors. One cistron, which was interpreted as an indication of chronic stress, moderated the relationships between academic stress and percentages of mature CD57⁺ NK cells. This chronic stress factor was also associated with an increment in memory and a decrease in naïve CD8 T cells and increased serum levels of IL-17. The present report identifies important potential psychological mediators of stress-induced changes in specific immunological parameters.

Commendation: Maydych V, Claus M, Dychus N, Ebel One thousand, Damaschke J, Diestel S, et al. (2017) Impact of chronic and acute academic stress on lymphocyte subsets and monocyte part. PLoS ONE 12(xi): e0188108. https://doi.org/10.1371/journal.pone.0188108

Editor: Fulvio d'Acquisto, Queen Mary University of London, UNITED KINGDOM

Received: July 7, 2017; Accepted: Nov ane, 2017; Published: November 16, 2017

Copyright: © 2017 Maydych et al. This is an open access article distributed under the terms of the Creative Eatables Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Data files.

Funding: The publication of this article was funded by the Open up Access Fund of the Leibniz Clan. The funders had no role in written report pattern, data drove and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have alleged that no competing interests exist.

Introduction

Stress is an integral function of modern life. Stressful situations contain a broad range of internal or ecology weather or events, eastward.yard. bereavement, caregiving for a relative with chronic disease, interpersonal conflicts, juggling many roles and responsibilities, task strain, unemployment, financial worries, over-exercising, and many others. Effects of psychological stress on immune functions have been demonstrated in numerous studies (for reviews see [1, 2]). Typical results include a reduction in the number and cytotoxicity of Natural Killer (NK) cells [3, 4], decreased percentages of CD4 helper T cells and CD8 cytotoxic T cells [five, 6], elevations of antibody titers to diverse herpes viruses [6, 7], equally well equally lower lymphocyte proliferation in response to specific mitogens [8, 9], all indicating detrimental effects on cellular immunity and immune function more than broadly. These effects vary depending on the blazon of stressor studied. Furthermore, studies differ in the immune parameters that are examined, which make the results rather difficult to compare. In addition, there might be inter-individual differences in psychological responsiveness to stress, which may moderate the result of stressful life experiences on allowed performance.

Bookish stress is one inquiry image used to investigate the furnishings of psychological stress on the immune organization [10]. Facing bookish examinations belongs to real-life challenges that induce a certain amount of stress in well-nigh individuals. Academic stress, in psychoneuroimmunological studies oftentimes referred to as a brief naturalistic stressor, can be conceptualized equally a blazon of stressor having both astute (e.grand. immediately before and during an exam) and prolonged characteristics (due east.grand. during the preparation or review period) [ii, 11]. Thus, academic examinations fall somewhere in-betwixt the continuum betwixt astute and chronic stress. Studies, which examine the relationship between examination stress and allowed parameters, ordinarily apply some repeated measurement design to compare the pre-examination and post-examination immune condition of students [7, 9, 12–15]. Well-nigh studies compare the baseline allowed status measured some weeks prior to examinations with the immune condition measured one day before or shortly after examinations. However, well-nigh studies practise not assess immune parameters during the extended periods of examination stress, namely during the anticipation of stress and the post-exam catamenia when waiting, possibly anxiously, for results.

Co-ordinate to contemporary conceptions of the nature of stress, 3 major components tin can exist distinguished: the presence of a stressor (1), subjective appraisal of this stressor every bit harmful or aversive (two), and the stress response (iii) [xvi]. While physical stressors elicit a stress response rather straight, psychological stressors first require a cognitive appraisal past the individual, which then elicits a response. Thus, depending on the subjective perception and interpretation of a stressor due to previous experiences and coping strategies, responses to stress tin can be different [17]. Based on inter-individual differences in reactivity to stress [18], information technology is obvious that immune responses to stress also vary betwixt people. Few studies investigated these inter-individual differences in immune functioning specifically with regard to the effects of brief naturalistic stress. For example, the frequency of engaging in relaxation exercise was shown to increase the percentages of T helper cells on the twenty-four hour period of an examination and result in higher numbers of T and B lymphocytes during the exam menses [15]. Poorer NK cell activeness during examinations could exist predicted by loneliness [19], emotional instability and high feet [20]. Psychological characteristics associated with resiliency may protect individuals against immune suppression or dysregulation in response to academic stress [21]. A potential function of further cognitive factors in immunological processes, including cognitive states and beliefs, is a relatively new and nether-investigated area in psychoneuroimmunology. Merely few studies accept systematically examined the role of affective and cognitive factors on immune responses during cursory naturalistic stress related to academic examinations. Considering psychological moderators of the stress-immunity relationship could shed light on mechanisms that are not captured by the main effects described in psychoneuroimmunology studies and may therefore assistance in clarifying some of the hitherto heterogeneous results.

The present written report was designed to see two objectives. Outset, we aimed at tracing the time form of eventual changes of immune functioning during an examination catamenia. Therefore, we employed a design with five repeated measurements covering not but the period of acute examination stress but also the pre- and post-examination period. We adamant several immune parameters, including total leukocyte counts, a phenotypic analysis of NK and T lymphocyte populations and measurements of cytokines.

2d, we were interested in possible modulations of stress-induced changes in immunological parameters by psychological factors. The psychological assessment in our report captured a series of psychometric questionnaires often used with regard to stress in work-related contexts. The traits and behavioral tendencies we measured were earlier shown to be associated with attenuation of negative effects of stress (i.e. active coping, expectation of success, self-control capacity), stress-related psychiatric diseases (i.eastward. depression), and stress-related states (ego depletion, general affective states) [22, 23]. Some psychological variables, depressive symptoms, burnout, positive and negative affect, active coping, emotional coping, and personal strain, take been previously reported to be related to allowed operation [24, 25]. Psychological scales ego depletion, capacity of self-control, expectation of success, and task demands have been taken into account on the ground of general theoretical considerations. To our knowledge, there is no study that was concerned with linking these psychological concepts from occupational psychology to immune parameters. In a wider context evidence of this kind of associations can help to evaluate and preclude stress-related health risks in the context of work. These analyses were primarily explorative in nature and should serve to guide future research delving deeper into the mechanisms by which psychological factors affect the responsiveness of the immune organization to stress.

Materials and methods

Participants

Study participants were 39 undergraduate students, recruited at the Ruhr Academy of Bochum, Germany. Participants were only included if they (a) fluently spoke German, (b) were not taking medication influencing immune functions, (c) were not significant, and (d) had no reported neuropsychological or psychiatric illnesses. They received either a full of 150€ or grade credits for their participation. Three students dropped out of the report. One participant was excluded because her/his Depressive Symptoms score was 3 standard deviations above the mean, indicating clinical depression. Another participant was excluded because her/his historic period was 2 standard deviations above the sample mean. As age is known to influence immunity, including this participant would accept distorted the homogeneity of our sample.

Furthermore, due to issues in blood sampling at private times of measurement, complete data sets could only be obtained from xx participants (85% female), ranging from 19 to 25 years of age (mean age 22.four, SD = 2.09). All subjects gave written informed consent to participate at the study. All procedures of the study were approved by the local ethics committee of the Leibniz Enquiry Centre for Working Environment and Human Factors.

Process

Participants arrived at the laboratory betwixt 9 a.g. and 2 p.thou. They first filled out a questionnaire that assessed their general health and health-related behaviors. Participants as well were asked whether they drank alcoholic beverages on the twenty-four hour period preceding the measurement. In the adjacent footstep, participants were asked to consummate a psychometric examination bombardment (encounter below). After completing questionnaires blood samples were fatigued.

Apart from the assessment of demographic variables (sex, age, field of written report), which took place just once, participants underwent the same procedure five times (Fig 1). The first ii sessions took identify 4.5 weeks and 1.5 weeks before the examination flow, at the showtime and at the terminate of January. The third session was scheduled for the first day of the examination period, in the middle of Feb. The last 2 sessions took place directly after and one week later on the test catamenia, at the end of February and at the commencement of March, respectively.

Fig i. Study pattern.

Study participants were one^st and 2^nd twelvemonth students studying at the Kinesthesia of Psychology (Ruhr-Academy Bochum, Germany). The commencement two sessions took identify 4.5 weeks and one.5 weeks before the examination catamenia, at the offset and at the stop of January. The third session was scheduled for the offset 24-hour interval of the test menstruation, in the eye of February. The last two sessions took place straight afterward and one week afterwards the examination menstruation, at the finish of Feb and at the beginning of March, respectively. Questionnaires were applied to assess general health and health-related behaviors and stress-related psychological parameters. Further, blood and saliva samples were taken.

https://doi.org/10.1371/journal.pone.0188108.g001

Psychological assessment

Without beingness committed to specific theoretical assumptions, for pragmatic reasons we conceptually distinguished betwixt more than stable or trait-like measures on the i manus and more state-like psychological measures on the other mitt [25]. Nosotros considered depressive symptoms, burnout, cocky-command chapters, job demands, and private strain as more than stable traits, which we expected not to be afflicted by examination stress. These scales were measured one time at session 1 and used as predictors for stress-related changes of immune parameters. On the other manus, the psychological variables ego depletion, full general melancholia states, agile and emotional coping, and expectation of success are related to emotional states, and can therefore vary due to various situational factors like, inter alia, test stress. We assessed these psychological state measures repeatedly. In the following, nosotros report detailed scales' descriptions and signal when these were measured.

Burnout.

The 2 burnout dimensions Emotional Exhaustion and Depersonalization were assessed past Büssing and Perrar'southward (1992) [26], German translation of the Maslach Exhaustion Inventory [27]. Burnout (nine items) addresses feelings of being overextended and drained by chore demands. This dimension was adapted to the academic domain (due east.m., 'I feel emotionally tuckered from my study'). Depersonalization (iv items) is characterized by a discrete, indifferent, and cynical attitude towards people with whom one has to interact at work. Two items of this dimension were also rephrased past using the word "study" instead of "work" (e.thousand., 'I have become more callous towards people since I am studying). All items are scored on a 6-signal rating scale (1 = non at all, half dozen = very strong). Exhaustion was measured once at session ane.

Depressive symptoms.

Depressive symptoms were measured with a shortened, German version of the Brook Depression Inventory [28]. The 15 items refer to diverse symptoms such equally sadness, reduced initiative, hopelessness, irritation, tiredness etc. [29]. Intensity/severity of symptoms is rated by a 6-signal frequency rating format (0 = never, five = very frequently). We assessed depressive symptoms once at session one.

General affective states.

We measured full general affective states using a German translation of the Positive and Negative Affect Schedule (PANAS) of [30]. Participants were asked to rate the intensity of experiencing each out of 20 emotions on a 5-indicate Likert Skale ranging from 1 (very slightly) to 5 (very much) in the terminal 12 months. Half of the presented emotion words chronicle to positive affect (due east.thou. alert, excited, enthusiastic, inspired, proud), the other half to negative touch on (eastward.g. upset, guilty, ashamed, irritable, scared). General affective states were measured at each session (five times in total).

Active coping.

Active coping was assessed by a custom vii items calibration phrased based on Latack and Havlovic (1992) [31] and roofing strategies aimed at creating favorable preconditions for meeting the demands addressed (eastward.grand. 'If something bothers me at my report, I try to switch it off as quickly as possible'; 'Earlier tackling hard tasks, I try to keep away from all possible disturbances'). All items are scored in a v-point Likert-rating format (one = not all, five = a great deal). The item scores were averaged to obtain a scale score. The internal consistency of that scale was α = .55. Active coping was assessed at each session (v times in full).

Expectation of success.

Expectation of success was measured with a custom scale of x items addressing expectations regarding the likelihood of (successfully) passing exams (e.yard. 'All in all I will succeed in upcoming exams'). All items were scored in a v-point intensity rating format (one = non at all, 5 = a dandy deal). The item scores were averaged to obtain a scale score. Cronbach'south alpha for this scale was α = .91. We measured expectation of success at sessions ane, 3 and 4.

Emotional coping.

Emotional coping was measured with a custom scale of 5 items referring to "managing the emotions that accompany the perception of stress" (east.1000. 'Even If I am extremely irritated of my study I try to stay calm and relaxed', 'I try to take pleasance fifty-fifty in unpleasant tasks in my study.' All items were scored on a v-bespeak Likert-rating format (i = not all, 5 = a great deal). The item scores were averaged to obtain a scale score. The internal consistency of that scale was α = .7. Emotional coping was assessed at each session (5 times in total).

Self-command chapters.

SCC equally an individual trait was measured past a German translation of the self-control scale developed by Tangney et al. (2004) [32, 33]. The scale concerns various aspects of self-control, in particular command over thoughts, emotional control, impulse control, functioning control, and habit breaking (due east.g. 'People would describe me as impulsive', 'I often interrupt people'). Participants were asked to rate items on a five-point rating calibration ranging from 1 (not at all) to v (very much). The internal consistency for this measure was α = .84. SCC was measured once at session 1.

Job demands.

Chore demands were assessed with items from the job scales developed past Prümper et al. (1995) [34]. 3 items refer to quantitative workload, addressing task demands like 'time pressure' and 'large amount of work'. three items refer to qualitative workload, consisting of statements referring to 'high demands on concentration' and 'high diverseness of tasks'. All items are scored on a 5-indicate rating format (1 = totally incorrect—5 = totally right). Participants were asked to signal the extent to which the respective statement applies to their studies on a five-signal Likert-calibration ranging from i (totally incorrect)–5 (totally right). The internal consistency for this measure was α = .83. Task demands were measured once at session one.

Private strain.

Private strain was measured by a 16 items custom scale based on Kanner et al. (1981) [35], covering strain related to dissimilar life domains like family (east.g. 'lack of fourth dimension for the family', 'troubles with children'), fiscal troubles (e.g. 'financial dubiety', 'financial responsibleness for others'), personal troubles (eastward.g. 'worries about health', 'worries about inner conflicts'). Respondents were first asked to signal whether they experienced the respective kind of trouble, and later on to indicate the severity to which they experienced information technology on a 4-point-scale ranging from 0 (non at all)– 4 (very severe). Cronbach's alpha for this scale was α = .65. Private strain was assessed once at session 1.

Biological assay

Saliva was collected to assess free cortisol concentrations [36] as a marker of HPA axis action. The samples were collected using Salivette sampling devices (Sarstedt, Nümbrecht, Germany). Participants collected saliva in the late evening (23:00h) and the side by side morning of the mean solar day following the university engagement. Saliva was collected upon awakening and thirty minutes later in guild to assess the cortisol awakening response [37]. Costless cortisol concentrations were analyzed without prior extraction using a commercial Chemoluminescence Immunoassay (CLIA; IBL International, Hamburg, Germany). All inter- and intra-assay variations were below 10%. A complete ready of cortisol data for all 5 session could be obtained from 29 participants.

Immunological phenotyping was performed using blood samples as recently described [38]. Using the methods described in this publication we adamant the absolute number of T cells, B cells, NK cells and monocytes in whole blood. Using menstruation cytometry we performed an analysis of NK and T lymphocyte subpopulations. We stimulated whole blood samples with Lipopolysaccharide (LPS) and measured the production of IL-6 and TNF-α. Finally, we determined the concentrations of cytokines in serum samples. The biological functions of the different immune parameters investigated in this study are detailed in a recent publication [38].

Statistical analyses

Initially, we confirmed that age was not correlated with whatever immunological parameter at whatsoever point of measurement. Therefore, age was not included as a control variable. Statistical analyses proceeded in several steps tailored to the study objectives every bit outlined above. In a first footstep, we analyzed stress-induced changes separately by repeated measurement analyses of variance (ANOVAs) with v levels of the within-participants variable Session and the respective immune parameter and salivary cortisol level equally the dependent variable. Nosotros applied Greenhouse-Geisser corrections where appropriate. Significant effects of Session were followed upward with Fisher's least significant difference tests (LSD).

In the second step, we analyzed stress-induced changes separately by repeated measurement analyses of variance (ANOVAs) with five levels of the within-participants variable Session and the psychological state variable as the dependent variable. We applied Greenhouse-Geisser corrections where advisable. Significant effects of Session were followed up with Fisher'due south to the lowest degree significant departure tests (LSD).

In a third step, nosotros submitted the questionnaire scales of the psychometric measurements to a Factor analyses. This analysis served two functions. Beginning, it facilitated the interpretation of our data. Second, we aimed at dealing with the problem of in role substantial inter-correlations among the psychometric measures equally detailed below.

In a fourth step, we analyzed inter-individual differences in stress-induced changes past 2x5 ANOVAs with dichotomized factor scores based on median splits and the five-level inside-participants variable representing Session that captured the time class of examination stress. Statistically significant interactions were followed up past tests of simple effects for the cess of statistical significance between groups on each level of the cistron Session and Fisher's least meaning difference (LSD) for cess of statistical significance between levels of the gene Session within each group.

In a 5th step, we computed correlations between psychometric predictors and immunological parameters or salivary cortisol levels at each individual session, as well every bit correlations between percentage change values of psychometric variables and percentage change values of both immunological parameters and salivary cortisol levels. Since session 1 took place prior to the showtime of the examination flow, the relationships to that point of fourth dimension were considered to imply some kind of basic inter-individual differences in immunity depending on psychological variables. Over again, correlations at Sessions 2 to 5 and correlations between pct modify values are assumed to reflect changes to the relationships betwixt immunological parameters, salivary cortisol levels, and psychological parameters under stress.

Results

To investigate the consequence of anticipated and astute stress on the immune organisation, we studied a group of healthy volunteers consisting of 39 undergraduate students of the Ruhr University Bochum in Germany. These students were undergoing a two-calendar week period where they had to complete several study exams. To investigate changes of the immune arrangement in preparation for, during, and subsequently this stressful test flow we examined the students at five unlike sessions over a flow of 8 weeks (Fig 1). In improver to a psychometric test bombardment, we took saliva samples to measure cortisol levels and blood samples to determine immunological parameters [38].

Cortisol levels at thirty minutes after awakening showed an increase during the first three sessions, which were before the test menstruation, and stayed loftier for the terminal two sessions after the exam menstruum (F(iv, 112) = 1.76 p = .142) (S1 Fig). The cortisol levels at the fourth dimension point of awakening (F(four, 112) = iii.05 p = .020; post-hoc LSD tests showed a significant increase from Session ii to Sessions 3 (p = .001) and five (p = .026), and a significant decrease from Session 3 to Session 4 (p = .026)) and the cortisol enkindling response (Machine) (F(4, 112) = 3.05 p = .020; post-hoc LSD tests demonstrated a significant increase from Session 1 to Sessions 2 (p = .013), 4 (p = .018) and 5 (p = .046)) did both evidence pregnant differences over the observation period. To compare our results with previous studies, we conducted additional 2x2 ANOVA with Session (session one = no examination stress, session 3 = exam stress) and absolute values of morning cortisol (enkindling, enkindling + thirty min) as within-subject factors. We found a trend towards a primary effect of session (F(1, 28) = 3.2; p = 0.085, r = .319), such that cortisol levels (awakening, awakening + 30 min) were higher at the examination stress session than at the non-stress session. The result size of r = .32 can exist gauged as a medium upshot of examination stress on cortisol which is in line with effects reported past others [39–41].

Analyzing the absolute numbers of lymphocytes and monocytes in the blood samples, we establish that the number of Natural Killer (NK) cells showed a significant subtract during the training menses (sessions 1–three) and stayed low later on the exam period (F(ii.650, 50.356) = iv.86 p = .006). LSD mail service-hoc tests demonstrated a significant mean difference between Sessions two and iv (p = .044) (Fig 2). We found a similar change for the number of monocytes, which showed its lowest value at the final session one week after the exam menstruation F(4, 76) = 6.71 (p = .000). LSD post-hoc tests demonstrated a significant hateful difference between Sessions 2 and v (p = .002). These changes were specific, as we did non find any significant changes in the absolute numbers of T- or B-lymphocytes (F_T (ii.982, 56.650) = ane.30 p = .282; F_B (4, 76) = 1.34 p = .263).

Fig 2. Changes in the absolute numbers of leukocytes.

The absolute numbers of T cells, B cells, NK cells and Monocytes were adamant in fresh whole blood past flow cytometry using TruCount Tubes. Data from each session are presented as means ± sem of twenty individual participants. Data were analyzed by repeated measures ANOVA. Data sets displaying significant differences between sessions are shown in black.

https://doi.org/10.1371/periodical.pone.0188108.g002

The immunophenotyping via catamenia cytometry allowed us to perform a more detailed analysis of the NK cells. This analysis revealed that in addition to the reduction in NK prison cell numbers, there was also a shift amongst the different NK cell subpopulations. We observed a significant reduction in the percentages of CD57⁺ (F(iv, 76) = 5.52 p = .001; post-hoc LSD tests demonstrated a significant decrease from Session ane to Sessions four (p = .005) and 5 (p = .004), a pregnant decrease from Session two to Sessions 4 (p = .001) and five (p = .004), and from Session iii to Sessions four (p = .020) and 5 (p = .045)) and KLRG1⁺ NK cells (F(4, 76) = iv.eleven p = .005; mail service-hoc LSD tests revealed a significant subtract from Session 1 to Session 5 (p = .029), a significant decrease from Session 2 to Sessions 4 (p = .029) and 5 (p = .022), and from Session three to Sessions four (p = .016) and 5 (p = .001)) when comparing the sessions before with the sessions after the exam menses (Fig 3A). Conversely, we found an increment in CD62L⁺ NK cells over the observation period (F(4, 76) = 5.93 p = .000; post-hoc LSD tests revealed a meaning increase from Session 1 to Sessions 4 (p = .002) and five (p = .001), a significant increase from Session 2 to Session four (p = .019), and from Session 3 to Sessions 4 (p = .007) and five (p = .006)). CD57 and KLRG1 are markers plant on more mature NK cell subpopulations, whereas CD62L marks the more immature NK cells [42]. This indicates that the exam period induced a shift from mature to more immature NK cells in the blood samples. Interestingly, we observed a similar shift towards more immature cells inside the T-lymphocyte compartment [43]. Over the ascertainment menstruation we detected an increment in the percentages of naïve CD4 T helper cells (F(iv, 76) = ii.97 p = .025; post-hoc LSD tests showed a significant decrease from Session 3 to Sessions 4 (p = .031) and v (p = .002)) and cytotoxic CD8 T cells (F(iv, 76) = ii.63 p = 0.41; post-hoc LSD tests showed a significant subtract from Session ii to Sessions 5 (p = .030)), while nosotros observed a slight decrease in CD4 effector memory cells (F(four, 76) = five.72 p = .000; mail-hoc LSD tests demonstrated a meaning decrease from Session i to Sessions 4 (p = .018) and v (p = .002), and a significant subtract from Session three to Sessions 4 (p = .012) and 5 (p = .000)) (Fig 3B).

Fig iii. Lymphocyte subsets and monocyte reactivity during the examination menstruum.

The relative size of lymphocyte subpopulations was analyzed by multicolor menstruum cytometry. All data are presented as means ± sem of 20 private participants. Data were analyzed by repeated measures ANOVA. Data sets displaying significant differences between sessions are shown in blackness. (A) NK cells (CD56+CD3- PBMC) were analyzed for the expression of CD57, KLRG1 and CD62L. (B) T cells (CD56-CD3+ PBMC) were pre-gated based on the expression of CD4 or CD8. Subpopulations were identified every bit CD45RA+CD62L+ (naive), CD45RA-CD62L+ (key memory) or CD45RA-CD62L- (effector retentivity). (C) Whole claret samples were treated for 3 h with LPS and samples were assayed for the production of IL-6 and TNF-α by monocytes. Data are presented every bit means ± sem of 20 individual participants. Data were analyzed past repeated measures ANOVA.

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Stimulation of blood samples with lipopolysaccharide (LPS) induces the release of pro-inflammatory cytokines by monocytes [44]. In our analysis this response increased during the observation period, reaching the highest release of IL-6 (F(2.545, 48.346) = 7.6 p = .001; post-hoc LSD tests revealed a significant decrease from Session 1 to Session 2 (p = .029), a significant increment from Session ane to Session four (p = .001), a pregnant increase from Session 2 to Sessions 3 (p = .023), four (p = .000) and five (p = .040), and a subtract from Session 4 to Session 5 (p = .002)) and TNF-α (F(iv, 76) = 5.9 p = .000; post-hoc LSD tests revealed a pregnant increase from Session 1 to Session 3 (p = .034), a significant increment from Session 2 to Sessions three (p = .013), four (p = .000) and v (p = .031), and a subtract from Session 4 to Session v (p = .039)) at session 4 directly at the finish of the examination period (Fig 3C). This is particularly interesting, equally we observed a reduction of monocyte numbers during the observation period (Fig ii). Therefore, the enhanced cytokine release is non due to an increase in cell numbers, but it must exist due to an enhanced reactivity of the monocytes. At session 5, ane week after the test period, both the monocyte numbers and the LPS-induced cytokine release showed a drop (Fig 3C).

We also analyzed the repeatedly measured psychometric scales in the participants for which a consummate prepare of immune parameters was bachelor. Only ego depletion showed a significant alter over the ascertainment period (F (iv, 72) = 4.062 p = .005). The hateful score significantly increased from Session ane to Session three (p = .010), and showed a decrease from Session 3 to Session five (p = .007), such that cocky-reported ego depletion achieved its maximum during the examination week and decreased after examinations (Fig 4A). Although non-pregnant, we observed a similar tendency for negative bear on. For emotional coping, agile coping, positive affect, and expectation of success, we observed a tendency towards a subtract from session 1 to session three with and an increase from session 3 to session 5. Notwithstanding, these changes were non significant.

Fig four. Immune parameters are associated with psychological variables.

(A) Mean score for ego depletion measured at session 1–5. (B) Participants were divided at the median of ego depletion calibration into high and depression ego depletion groups. Data are presented as mean ± sem of 20 individual participants. (C) T cells were identified as CD56-CD3+ PBMC. The pct of CD4+CD28- cells was associated with the reported level of emotional exhaustion at session one. Information are presented as mean of 20 individual participants. Information were analyzed past correlation analyses.

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Next nosotros were interested to clarify possible relationships between the immunological and psychometric variables. When looking at the drop of NK cell numbers in the blood samples during the observation period, we noticed an interesting trend. NK prison cell numbers seemed to be unlike between participants reporting high ego depletion compared to individuals with low ego depletion. The driblet in NK cell numbers during the observation menstruum was only evident in individuals with low ego depletion, as participants with high ego depletion seemed to take already lower NK cell numbers at session i (Fig 4B). Although the difference failed to reach significance in our comparatively small sample size (F(4, 72) = ii.2 p = 0.078) mail-hoc tests revealed meaning mean differences between the NK jail cell counts in depression and loftier ego depletion group at session one(p = .022) and as well at session 3 (p = .022), indicating that an interaction trend we found for NK cell counts and ego depletion is non solely due to the baseline differences at session one. More than important, session-wise mean comparisons within each group showed a significant decline of NK jail cell counts from Sessions 1 and ii to Sessions 4 and v (1 to four p = .028; 1 to 5 p = .03; 2 to 4 p = .047) for the low ego depletion group, and no pregnant changes in the loftier ego depletion group.

An increase in CD28 negative T cells has been associated with chronic inflammatory conditions [45]. Interestingly, we observed a significant correlation betwixt the percentage of CD28 negative CD4 T cells and emotional burnout (r = .l p = .025) (Fig 4C).

Our psychometric measures determined different facets of chronic and acute stress as well as coping with stress. This inevitably yielded a number of measures that were in part highly intercorrelated. Therefore, we aggregated our psychological variables by means of a Factor Analysis (FA). We submitted participants' mean scores on the scales Emotional Burnout, Depersonalization, Depressive Symptoms, Cocky-control Capacity, Expectation of Success, Agile Coping, Ego Depletion, Negative Affect, Positive Affect, and Emotional Coping to a principal components analysis (PCA) with orthogonal VARIMAX rotation. This yielded a 2-cistron solution accounting for 63% of the variance. Table i summarizes the loadings of all variables on the two uncorrelated factors. According to the observed pattern, factor i lends itself to an interpretation in terms of chronic stress. Thus, variables being commonly associated with chronic stress like Emotional Exhaustion, Depersonalization, Depressive Symptoms, Ego Depletion, and Negative Affect load positively on this factor with weights > .46, while Positive Affect and Emotional Coping load with high negative weight on this factor. This outset factor accounted for 31.ix% of the variance.

Factor two, which is characterized by big positive loadings of the scales Self-control Capacity, Expectation of Success, and Coping (all > .five), as well as moderately positive loadings of Positive Affect and Emotional Coping and moderately negative loadings of Emotional Burnout and Depressive Symptoms, suggests an interpretation in terms of the potential to effectively cope with stress. This factor deemed for 31.one% of the variance.

We did not notice any systematic relationships between gene 1 psychometric score and changes over time of salivary cortisol measures. Changes over time in isolated psychometric scores also did not show whatsoever systematic relationships to cortisol levels. Next we investigated relationships between the immunological parameters and the 2 factors of the aggregated psychological variables. Factor 2 ('constructive coping with stress') was not significantly correlated with immunological parameters. In contrast, we found that factor 1 ('chronic stress') had an impact on the shift towards more immature lymphocytes during the observation period. The reduction of the more than mature CD57⁺ NK cells was more than pronounced in participants with a loftier score on factor one (Fig 5A), suggesting that the acute stress of the exam catamenia had more impact on individuals with higher chronic stress (F(4, 72) = 2.viii p = .04). We observed no significant mean differences betwixt low and high chronic stress grouping for %CD57 NK cells at any session. Session-wise mean comparisons within each group showed a significant reject of % CD57 NK cells from Session 3 to Session five (p = .011) in the low factor i group, and a significant decline of % CD57 NK cells from Session 1 to Session four (p = .001), from Session 1 to Session 5 (p = .020), from Session, from Session 2 to Session 4 (p = .000), and from Session two to Session 5 (p = .043) in the loftier chronic stress group. Similarly, we observed a correlation betwixt factor i and the proportion of naïve versus memory CD8 T cells. Already at session ane the percentage of central (r = -.48 p = .034) and effector memory CD8 T cells (r = -.56 p = .010) was negatively correlated to factor 1 (Fig 5B and 5C). Therefore, loftier chronic stress seems to be correlated with a reduction in retentivity CD8 T cells. Conversely, nosotros observed a trend towards a positive correlation between factor ane and naïve CD8 T cells at session 1 (r = .38 p = .103) (Fig 5D). This correlation between the ratio of memory versus naïve CD8 T cells and cistron 1 was withal detectable at session 4 directly after the exam period (r_{CD8central retentivity} = -.34 p = .146; r_{CD8 effector retentiveness} = -.64 p = .003; r_{CD8 naive} = .52 p = .019) (Fig 5B–5D).

Fig five. Association of maturation markers and inflammatory cytokines with chronic stress.

(A) Participants were divided at the median score of Factor 1 into high and low Cistron i groups. Data are presented as mean ± sem of xx individual participants. Data were analyzed by 2x5 ANOVA with Factor 1 as between-participants factor and the five-level within-participants factor representing Session. CD8+ T cell subpopulations were identified every bit described in Fig iii. Percentage of cardinal memory (B), effector memory (C) and naive (D) CD8 T cells at sessions 1 and iv was associated with Gene i. Data were analyzed by correlation analyses. Data from 20 participants are shown. (E) Serum concentration of IL-17 at sessions 1 and four was associated with Factor 1. Data were analyzed past correlation analyses.

https://doi.org/10.1371/periodical.pone.0188108.g005

Chronic stress has been associated with increased levels of pro-inflammatory cytokines [46]. In our analysis we constitute a positive correlation between the factor 1 and an increase in serum IL-17 levels (Fig 5E). Factor 1 and serum IL-17 levels correlated both at session 1 (r = .73 p = .000) and at session 4 (r = .45 p = .047), suggesting that chronic stress had a stronger touch on IL-17 levels then the astute stress of the exam period.

Discussion

In the current study we used academic stress every bit a naturalistic stressor to investigate the furnishings of psychological stress on a broad range of immune parameters and assessed psychological variables associated with chronic stress and coping. Our objective was to investigate how examination stress will touch on the allowed response and whether these effects would be influenced by psychological variables.

Results indicated that absolute salivary cortisol levels measured subsequently awakening and thirty minutes later awakening increased during examinations compared to the not-test menstruation. Although the elevation was meaning only for cortisol levels later enkindling, the pattern we observed was at least partially in line with existing information from examination stress protocol studies [39, 40, 47]. Indeed, the estimated effect size for absolute cortisol levels elevations was medium and also in accord with previous inquiry [39, 40, 47]. Given the small and homogeneous sample size, and possible confounders (east.thousand. season, sleep duration), we cannot reliably judge the severity of stress added during examination stress. Contrary to our expectation, nosotros observed a pregnant subtract of Motorcar. This is about probable due to the fact that an acme of cortisol levels was more pronounced for the time after enkindling and non for the time 30 minutes afterward awakening, and CAR was calculated as a deviation between the cortisol levels after awakening and cortisol levels 30 minutes afterwards awakening.

The decrease in the absolute numbers of NK cells is consistent with previous studies [i] and has been associated with chronic stress [48, 49]. Nonetheless, the shift from mature to more immature NK cell subpopulations in peripheral blood has not been reported so far. This suggests that the brief naturalistic stressor results in a redistribution of specific lymphocyte subsets. Mature NK cells are likely being recruited into the tissue or attach to the endothelium, which would explicate the reduction in NK cell numbers and the shift towards an increased proportion of immature NK cells. We recently showed that the activation of the integrin LFA-1 is enhanced in mature NK cells, which would support their preferential adhesion and redistribution from the claret into tissues [50]. This lymphocyte redistribution could be interpreted as a functional response to recruit effector cells to locations where they may be needed in case of injury and infection.

Interestingly, we observed a like redistribution towards more naïve cells in the T cell compartment. This suggests that a mobilization of mature and memory lymphocytes may be a general response towards stress. This is also supported past our finding that cistron i, equally a parameter for chronic stress, was also correlated with a shift towards more naïve and less memory CD8 T cells.

The reduction in monocyte numbers could similarly be a result of the redistribution of these cells from the blood into the tissue. Yet, we also detected an increased functionality of these cells. Therefore, despite lower monocyte numbers we detected more than LPS-induced production of IL-six and TNF-α in response to the test stress. Therefore, a cursory naturalistic stressor may boost the functionality of monocytes. Monocyte responses are important for immune reactions against bacterial infections and NK cells and cytotoxic T cells are necessary for the defence against viral infections. Therefore, the redistribution of these cells towards possible sites of injury and infection and the enhanced part of monocytes may exist a manner to boost the immune system in response to the brief stressor and to protect the individual from infections. Interestingly, anticipatory stress as in the example of a preparation for an important test has been associated with an allowed-mediated protection from infection [51, 52]. Individuals are often able to work with high performance fifty-fifty if they are already in poor health, and and so fall sick when the of import examination is over [53]. We observed a drop in monocyte numbers and functionality in the last sample, i week after the exam menstruum, which may bespeak that the boost in immune function is reduced at this time signal.

We assumed that there might besides be individual differences beyond the exam period as a result of personality characteristics related stress and coping that may influence the immune parameters. Therefore, we tested for such relationships and obtained numerous correlations between immunological parameters and psychological variables. Factor i, which represents variables unremarkably associated with chronic stress, positively correlated with serum levels of interleukin IL-17, which is secreted by Th17 cells. Th17 cells are important for immune responses against infections, specially at mucosal surfaces. However, they are also associated with autoimmune diseases and chronic inflammatory disorders [54–56]. Th17 cells have non been investigated in chronic stress models so far. As psychological stress is associated with chronic inflammation, Th17 might be 1 of the biological links between chronic stress and inflammation. Previous studies reported that brief naturalistic stress can crusade a shift from Th1 cytokines towards Th2 cytokines [2]. Nosotros did non observe such a shift in our data. On explanation for this discrepancy may exist that other studies [12] measured cytokine concentrations later ex vivo stimulation of claret samples, while we measured cytokine levels in serum without stimulation.

Our data illustrate that psychological variables assessed via cocky-report (i.a. earlier experienced stress) influence the magnitude of immune reactivity induced by brief naturalistic stress. High level of chronic stress (as subsumed under cistron 1) was associated with the reduction in the percentage of mature CD57⁺ NK cells, whereas no such clan could be observed in the group with low level of chronic stress. This effect is partially consistent with the study of Brosschot et al. that showed a greater reduction of the pct of mature CD57⁺ NK cells during the stress situation in individuals with greater life stress [57]. Although the results of Brosschot et al. refer to allowed reactivity to acute laboratory stressor, and chronic stress was conceptualized in terms of daily hassles in the concluding 2 months, at that place was some consistency in the results indicating that accumulated stress could alter the vulnerability of the private to psychological stressors, which normally would not change the immune status.

In contrast, the drop in absolute NK cell numbers was more pronounced in individuals with depression ego depletion. In individuals experiencing high levels of ego depletion the absolute NK numbers were already at a lower level and did not decrease much further. Interestingly, ego depletion was the simply psychological variables intended to capture psychological states, which exhibited a clear-cut dependence on the fourth dimension course of examination stress. In experimental and social psychology ego depletion refers to a state of impaired cocky-control. In particular, ego depletion effects were offset demonstrated in experimental procedures using cocky-control tasks. The performance of participants who were required to appoint in a self-control task earlier in the experiment was poorer relative to a control group which was not engaged in a self-control task in the first stage but performed a control job not related to self control instead [58, 59]. Furthermore, enquiry has also shown that self-reported ego depletion was associated with increased perceptions of fatigue, effort, negative mood, and reduced glucose claret level [run across [60] for review].

From an ecological immunology perspective, organismic free energy availability impacts immune function due to energetic demands of immunity [61]. Equally fauna models show, caloric restriction and reductions in torso fat led to suppression of immune functions and increased hazard of infections [62]. Interpreting our finding in this line would mean that high ego depletion results in lower energy levels in the body. As a consequence, NK cell-amnesty may be suppressed in order to preserve energetic costs. Inadequate stress response to exam stress equally a result of earlier experienced stress in highly ego depleted individuals could exist some other explanation of our results [63]. To our knowledge, at that place accept been no studies addressing the relationship betwixt ego depletion and NK cell numbers.

In addition, our data bear witness that these psychological characteristics might be relevant not only in a stress context simply also for predicting basal immune status [64]. Therefore, because the impact of personality characteristics in the future tin can contribute to better agreement of personality driven immunity, and information technology can assist to identify the responsible mechanisms.

There were no systematic associations between cortisol levels and subjective chronic stress feel every bit captured by Factor 1. We neither detected systematic meaning correlations betwixt per centum alter values from ego depletion and percentage change values from three cortisol measures (wakening, wakening +thirty and CAR) at sessions 1 and 3, and 5 and 3, such equally elevations in cortisol seem to be independent from of psychological measures. We cannot completely delineate the causes for these results, because they can exist due to other biochemical mechanisms underlying psychological stress-related measures. Another possible caption is that questionnaires on stress-related psychological measures are not a expert measure for subjective stress experience [39, 47]. The studies on the extent to which psychological stress measures are predictive for cortisol reactivity have also demonstrated inconsistent results [41].

Limitations

Our study has several limitations. Showtime, we were able to obtain consummate data sets from simply a relatively pocket-size sample of participants. This restriction may be responsible for null findings (reduced power). Likewise, nosotros examined a rather large number of variables, which inevitably entails a risk of imitation positives. Our use of cistron analysis reduced this problem at to the lowest degree on the psychological side. Nevertheless, one should be aware that, in line with the exploratory nature of these analyses, our findings should exist considered as tentative and are in need of replication. 2nd, reflecting the gender distribution amid psychology students in Germany, 85% of our participants were female person which is problematic for the generalizability of our results. Gender may moderate the furnishings of stress on immunity by virtue of the effects of sex activity hormones on immunity [ii]. Studies demonstrated that men are considered to be more biologically vulnerable [65]. Furthermore, although nosotros controlled for health status, additional environmental factors, such as seasonal influences or reduced sleep duration, could have interfered with the results. Still, despite these limitations, we believe that our study makes a significant contribution to understanding the furnishings of naturalistic stress on several immune functions including NK and T prison cell subsets.

Supporting information

S1 Fig. Cortisol response during study menstruum.

Cortisol concentration in saliva was measured in the evening every bit control, after awakening, and thirty min after awakening. Further, Cortisol Awakening Response (Auto) was calculated. Data are presented as mean ± sem of 29 individual participants for which a complete set of cortisol concentration data was bachelor. Data were analyzed by repeated measures ANOVA.

https://doi.org/ten.1371/periodical.pone.0188108.s001

(TIF)

Acknowledgments

We would like to thank all volunteer participants of this study and Manfred Schedlowski for his discussions and the critical reading of the manuscript. The publication of this article was funded by the Open up Admission Fund of the Leibniz Clan.

References

1. i. Herbert TB, Cohen S. Stress and immunity in humans: a meta-analytic review. Psychosom Med. 1993;55(four):364–79. pmid:8416086.
   • View Article
   • PubMed/NCBI
   • Google Scholar
2. 2. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic report of thirty years of inquiry. Psychol Balderdash. 2004;130(4):601–30. pmid:15250815; PubMed Central PMCID: PMC1361287.
   • View Article
   • PubMed/NCBI
   • Google Scholar
3. three. Glaser R, Rice J, Speicher CE, Stout JC, Kiecolt-Glaser JK. Stress depresses interferon product by leukocytes concomitant with a decrease in natural killer cell activity. Behav Neurosci. 1986;100(5):675–8. pmid:2430594.
   • View Article
   • PubMed/NCBI
   • Google Scholar
4. 4. Irwin M, Patterson T, Smith TL, Caldwell C, Brown SA, Gillin JC, et al. Reduction of allowed role in life stress and depression. Biol Psychiatry. 1990;27(1):22–30. pmid:2297549.
   • View Article
   • PubMed/NCBI
   • Google Scholar
5. 5. Glaser R, Kiecolt-Glaser JK, Stout JC, Tarr KL, Speicher CE, Holliday JE. Stress-related impairments in cellular immunity. Psychiatry Res. 1985;16(iii):233–nine. pmid:2935896.
   • View Commodity
   • PubMed/NCBI
   • Google Scholar
6. 6. Kiecolt-Glaser JK, Glaser R, Shuttleworth EC, Dyer CS, Ogrocki P, Speicher CE. Chronic stress and immunity in family unit caregivers of Alzheimer'south disease victims. Psychosom Med. 1987;49(v):523–35. pmid:3671639.
   • View Article
   • PubMed/NCBI
   • Google Scholar
7. 7. Glaser R, Pearl DK, Kiecolt-Glaser JK, Malarkey WB. Plasma cortisol levels and reactivation of latent Epstein-Barr virus in response to examination stress. Psychoneuroendocrinology. 1994;19(8):765–72. pmid:7991763.
   • View Article
   • PubMed/NCBI
   • Google Scholar
8. 8. Dobbin JP, Harth Chiliad, McCain GA, Martin RA, Cousin Yard. Cytokine production and lymphocyte transformation during stress. Encephalon Behav Immun. 1991;5(4):339–48. pmid:1777728.
   • View Article
   • PubMed/NCBI
   • Google Scholar
9. nine. Halvorsen R, Vassend O. Effects of Examination Stress on Some Cellular-Immunity Functions. Journal of Psychosomatic Research. 1987;31(6):693–701. PubMed PMID: WOS:A1987L361800004. pmid:2963118
   • View Commodity
   • PubMed/NCBI
   • Google Scholar
10. 10. Stowell JR. Utilize and abuse of academic examinations in stress research. Psychosomatic Medicine. 2003;65(vi):1055–7. PubMed PMID: WOS:000186872400018. pmid:14645785
    • View Article
    • PubMed/NCBI
    • Google Scholar
11. 11. Preuss D, Schoofs D, Schlotz Due west, Wolf OT. The stressed pupil: influence of written examinations and oral presentations on salivary cortisol concentrations in university students. Stress. 2010;13(iii):221–9. pmid:20235829.
    • View Article
    • PubMed/NCBI
    • Google Scholar
12. 12. Marshall GD Jr., Agarwal SK, Lloyd C, Cohen L, Henninger EM, Morris GJ. Cytokine dysregulation associated with exam stress in salubrious medical students. Brain Behav Immun. 1998;12(4):297–307. pmid:10080859.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
13. thirteen. Katsuura Due south, Kamezaki Y, Tominaga M, Masuda K, Nishida K, Yamamoto Y, et al. High-throughput screening of brief naturalistic stress-responsive cytokines in academy students taking examinations. Int J Psychophysiol. 2010;77(two):135–40. pmid:20483365.
    • View Article
    • PubMed/NCBI
    • Google Scholar
14. fourteen. Hoglund CO, Axen J, Kemi C, Jernelov S, Grunewald J, Muller-Suur C, et al. Changes in immune regulation in response to examination stress in atopic and salubrious individuals. Clin Exp Allergy. 2006;36(viii):982–92. pmid:16911354.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
15. fifteen. Kiecolt-Glaser JK, Glaser R, Strain EC, Stout JC, Tarr KL, Holliday JE, et al. Modulation of cellular immunity in medical students. J Behav Med. 1986;ix(1):v–21. pmid:2939253.
    • View Article
    • PubMed/NCBI
    • Google Scholar
16. sixteen. Steckler T. The neuropsychology of stress. Techniques in the Behavioral and Neural Sciences. 152005. p. 25–42.
    • View Article
    • Google Scholar
17. 17. Goldstein DS. The autonomic nervous organisation in wellness and affliction. New York: K. Dekker; 2001. xii, 618 p. p.
18. 18. McEwen BS, Stellar E. Stress and the private. Mechanisms leading to disease. Arch Intern Med. 1993;153(18):2093–101. pmid:8379800.
    • View Article
    • PubMed/NCBI
    • Google Scholar
19. nineteen. Kiecolt-Glaser JK, Garner West, Speicher C, Penn GM, Holliday J, Glaser R. Psychosocial modifiers of immunocompetence in medical students. Psychosom Med. 1984;46(ane):vii–fourteen. pmid:6701256.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
20. 20. Borella P, Bargellini A, Rovesti Due south, Pinelli M, Vivoli R, Solfrini V, et al. Emotional stability, feet, and natural killer activity under examination stress. Psychoneuroendocrinology. 1999;24(6):613–27. pmid:10399771.
    • View Article
    • PubMed/NCBI
    • Google Scholar
21. 21. Segerstrom SC, Taylor SE, Kemeny ME, Fahey JL. Optimism is associated with mood, coping, and immune change in response to stress. Journal of Personality and Social Psychology. 1998;74(half dozen):1646–55. PubMed PMID: WOS:000074328700018. pmid:9654763
    • View Article
    • PubMed/NCBI
    • Google Scholar
22. 22. Schmidt KH, Hupke G, Diestel S. Does dispositional chapters for cocky-control attenuate the relation between self-control demands at piece of work and indicators of job strain? Work and Stress. 2012;26(1):21–38. PubMed PMID: WOS:000302565700002.
    • View Article
    • Google Scholar
23. 23. Schmidt KH, Diestel Due south. Cocky-Command Demands From Basic Inquiry to Job-Related Applications. Periodical of Personnel Psychology. 2015;14(1):49–sixty. PubMed PMID: WOS:000356028700007.
    • View Article
    • Google Scholar
24. 24. Olff M. Stress, depression and immunity: the office of defence and coping styles. Psychiatry Res. 1999;85(1):7–15. PubMed PMID: WOS:000080236100003. pmid:10195312
    • View Article
    • PubMed/NCBI
    • Google Scholar
25. 25. Hamaker EL, Nesselroade JR, Molenaar PCM. The integrated trait-state model. Journal of Research in Personality. 2007;41(ii):295–315. PubMed PMID: WOS:000245966400003.
    • View Commodity
    • Google Scholar
26. 26. Büssing A, Perrar Yard-M. Dice Messung von Exhaustion. Untersuchung einer deutschen Fassung des Maslach Exhaustion Inventory (MBI-D). Diagnostica. 1992.
27. 27. Maslach C, Jackson SE. The measurement of experienced exhaustion. Periodical of organizational behavior. 1981;2(2):99–113.
    • View Article
    • Google Scholar
28. 28. Brook AT, Steer RA, Carbin MG. Psychometric properties of the Brook Low Inventory: Twenty-v years of evaluation. Clinical psychology review. 1988;eight(1):77–100.
    • View Article
    • Google Scholar
29. 29. Schmitt M, Maes J. Vorschlag zur Vereinfachung des Brook-Depressions-Inventars (BDI) [Simplification of the Beck-Low-Inventory (BDI)]. Diagnostica. 1999;46(i):38–46.
    • View Article
    • Google Scholar
30. thirty. Watson D, Clark LA, Tellegen A. Development and validation of cursory measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988;54(6):1063–70. pmid:3397865.
    • View Article
    • PubMed/NCBI
    • Google Scholar
31. 31. Latack JC, Havlovic SJ. Coping with job stress: A conceptual evaluation framework for coping measures. Periodical of organizational beliefs. 1992;13(5):479–508.
    • View Article
    • Google Scholar
32. 32. Tangney JP, Baumeister RF, Boone AL. High cocky-command predicts good adjustment, less pathology, meliorate grades, and interpersonal success. J Pers. 2004;72(two):271–324. pmid:15016066.
    • View Article
    • PubMed/NCBI
    • Google Scholar
33. 33. Neubach B, Schmidt K-H. Selbstkontrolle als Arbeitsanforderung-Rekonzeptualisierung und Validierung eines Messinstruments [Self-control as a job need—development and validation of a measurement instrument]. Zeitschrift für Arbeits-und Organisationspsychologie. 2006;fifty(2):103–9.
    • View Commodity
    • Google Scholar
34. 34. Prümper J, Hartmannsgruber K, Frese M. KFZA. Kurz-Fragebogen zur Arbeitsanalyse [KFZA—A brusk questionnaire for job analysis]. Zeitschrift für Arbeits-und Organisationspsychologie. 1995;39(3):125–31.
    • View Article
    • Google Scholar
35. 35. Kanner Advertising, Coyne JC, Schaefer C, Lazarus RS. Comparison of ii modes of stress measurement: Daily hassles and uplifts versus major life events. Periodical of behavioral medicine. 1981;4(1):1–39. pmid:7288876
    • View Article
    • PubMed/NCBI
    • Google Scholar
36. 36. Kirschbaum C, Hellhammer DH. Salivary cortisol in psychoneuroendocrine research: recent developments and applications. Psychoneuroendocrinology. 1994;xix(4):313–33. pmid:8047637.
    • View Article
    • PubMed/NCBI
    • Google Scholar
37. 37. Pruessner JC, Wolf OT, Hellhammer DH, Buske-Kirschbaum A, von Auer K, Jobst Southward, et al. Free cortisol levels after awakening: a reliable biological marker for the cess of adrenocortical activity. Life Sci. 1997;61(26):2539–49. pmid:9416776.
    • View Article
    • PubMed/NCBI
    • Google Scholar
38. 38. Claus M, Dychus Northward, Ebel Chiliad, Damaschke J, Maydych V, Wolf OT, et al. Measuring the immune organisation: a comprehensive approach for the analysis of immune functions in humans. Arch Toxicol. 2016;90(10):2481–95. pmid:27522652.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
39. 39. Weekes N, Lewis R, Patel F, Garrison-Jakel J, Berger DE, Lupien SJ. Examination stress as an ecological inducer of cortisol and psychological responses to stress in undergraduate students. Stress-the International Journal on the Biological science of Stress. 2006;9(4):199–206. PubMed PMID: WOS:000244247900002. pmid:17175505
    • View Article
    • PubMed/NCBI
    • Google Scholar
40. 40. Weekes NY, Lewis RS, Goto SG, Garrison-Jakel J, Patel F, Lupien South. The effect of an environmental stressor on gender differences on the awakening cortisol response. Psychoneuroendocrinology. 2008;33(6):766–72. PubMed PMID: WOS:000258356200007. pmid:18541385
    • View Article
    • PubMed/NCBI
    • Google Scholar
41. 41. Tater L, Denis R, Ward CP, Tartar JL. Academic stress differentially influences perceived stress, salivary cortisol, and immunoglobulin-A in undergraduate students. Stress-the International Journal on the Biology of Stress. 2010;13(4):366–71. PubMed PMID: WOS:000280146300009. pmid:20536338
    • View Article
    • PubMed/NCBI
    • Google Scholar
42. 42. Geiger TL, Sun JC. Development and maturation of natural killer cells. Curr Opin Immunol. 2016;39:82–9. pmid:26845614; PubMed Central PMCID: PMCPMC4801705.
    • View Article
    • PubMed/NCBI
    • Google Scholar
43. 43. Xu W, Larbi A. Markers of T Cell Senescence in Humans. Int J Mol Sci. 2017;18(8). pmid:28796199; PubMed Fundamental PMCID: PMCPMC5578132.
    • View Article
    • PubMed/NCBI
    • Google Scholar
44. 44. Key J, Pretorius CJ, Ungerer JP. Biological and diurnal variation in glucocorticoid sensitivity detected with a sensitive in vitro dexamethasone suppression of cytokine production analysis. J Clin Endocrinol Metab. 2010;95(8):3657–63. pmid:20463096.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
45. 45. Mou D, Espinosa J, Lo DJ, Kirk Advert. CD28 negative T cells: is their loss our gain? American Journal of Transplantation. 2014;14(11):2460–six. pmid:25323029
    • View Article
    • PubMed/NCBI
    • Google Scholar
46. 46. Hänsel A, Hong S, Cámara RJ, Von Kaenel R. Inflammation as a psychophysiological biomarker in chronic psychosocial stress. Neuroscience & Biobehavioral Reviews. 2010;35(1):115–21.
    • View Article
    • Google Scholar
47. 47. Lupien SJ, McEwen BS. The acute effects of corticosteroids on noesis: Integration of brute and homo model studies. Brain Res Rev. 1997;24(1):1–27. PubMed PMID: WOS:A1997XM00800001. pmid:9233540
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
48. 48. Nakamura H, Nagase H, Yoshida Grand, Ogino K. Natural killer (NK) cell activeness and NK cell subsets in workers with a tendency of burnout. J Psychosom Res. 1999;46(6):569–78. pmid:10454173.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
49. 49. De Gucht V, Fischler B, Demanet C. Immune dysfunction associated with chronic professional stress in nurses. Psychiatry Res. 1999;85(1):105–11. pmid:10195321.
    • View Article
    • PubMed/NCBI
    • Google Scholar
50. l. Urlaub D, Hofer Yard, Muller ML, Watzl C. LFA-1 Activation in NK Cells and Their Subsets: Influence of Receptors, Maturation, and Cytokine Stimulation. J Immunol. 2017;198(five):1944–51. pmid:28100681.
    • View Article
    • PubMed/NCBI
    • Google Scholar
51. 51. Slattery Chiliad, Grieve A, Paletz Due east, Kalin North. 157. Anticipatory stress appraisal is differentially associated with HPA and immune acute stress responses in children with anxiety disorders. Encephalon, Behavior, and Immunity. 2012;26:S44.
    • View Article
    • Google Scholar
52. 52. Wirtz PH, von Kanel R, Emini L, Suter T, Fontana A, Ehlert U. Variations in anticipatory cognitive stress appraisement and differential proinflammatory cytokine expression in response to astute stress. Brain Behav Immun. 2007;21(vi):851–9. pmid:17412556.
    • View Article
    • PubMed/NCBI
    • Google Scholar
53. 53. Van Heck GL, Vingerhoets AJ. Leisure sickness: a biopsychosocial perspective. Psihologijske teme. 2007;16(2):178–200.
    • View Article
    • Google Scholar
54. 54. Waite JC, Skokos D. Th17 response and inflammatory autoimmune diseases. Int J Inflam. 2012;2012:819467. pmid:22229105; PubMed Central PMCID: PMCPMC3249891.
    • View Article
    • PubMed/NCBI
    • Google Scholar
55. 55. Yang J, Sundrud MS, Skepner J, Yamagata T. Targeting Th17 cells in autoimmune diseases. Trends Pharmacol Sci. 2014;35(10):493–500. pmid:25131183.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
56. 56. Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012;11(x):763–76. pmid:23023676.
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
57. 57. Brosschot JF, Benschop RJ, Godaert G, Olff Yard, De Smet M, Heijnen CJ, et al. Influence of life stress on immunological reactivity to mild psychological stress. Psychosom Med. 1994;56(3):216–24. pmid:8084967
    • View Article
    • PubMed/NCBI
    • Google Scholar
58. 58. Baumeister RF, Vohs KD. Self-regulation, ego depletion, and motivation. Social and Personality Psychology Compass. 2007;i(1):115–28.
    • View Article
    • Google Scholar
59. 59. Baumeister RF, Vohs KD, Tice DM. The strength model of cocky-control. Current Directions in Psychological Scientific discipline. 2007;16(half-dozen):351–v. PubMed PMID: WOS:000251186100013.
    • View Article
    • Google Scholar
60. 60. Hagger MS, Woods C, Strong C, Chatzisarantis NLD. Ego Depletion and the Strength Model of Self-Control: A Meta-Analysis. Psychol Bull. 2010;136(4):495–525. PubMed PMID: WOS:000279187100004. pmid:20565167
    • View Article
    • PubMed/NCBI
    • Google Scholar
61. 61. Segerstrom SC. Resource, stress, and immunity: An ecological perspective on homo psychoneuroimmunology. ‎Ann Behav Med. 2010;forty(1):114–25. pmid:20526755
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
62. 62. Demas GE. The energetics of immunity: a neuroendocrine link betwixt energy balance and allowed function. Horm Behav. 2004;45(3):173–80. PubMed PMID: WOS:000220686500003. pmid:15047012
    • View Article
    • PubMed/NCBI
    • Google Scholar
63. 63. McEwen BS. Stress, accommodation, and affliction: Allostasis and allostatic load. Ann Due north Y Acad Sci 1998;840(1):33–44.
    • View Article
    • Google Scholar
64. 64. Cohen South, Janicki-Deverts D, Crittenden CN, Sneed RS. Personality and human immunity. The Oxford Handbook of Psychoneuroimmunology: Oxford University Press Inc.; 2012.
65. 65. Pehlivanoglu B, Balkanci ZD, Ridvanagaoglu AY, Durmazlar North, Ozturk M, Erbas D, et al. Bear on of stress, gender and menstrual cycle on immune system: possible role of nitric oxide. Arch Physiol Biochem. 2001;109(4):383–7. Epub 2002/04/06. pmid:11935378.
    • View Article
    • PubMed/NCBI
    • Google Scholar

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Source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188108

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