Validation of the irritation scale on a representative German sample: new normative data.

The irritation scale is a widely used and reliable self-report scale for measuring cognitive and emotional strain related to the work environment. It extends existing measures by providing a sensitive assessment for pre-clinical stress at work. Existing normative data are based on convenience samples and are therefore not representative. This study provides new normative data for the irritation scale based on a representative German sample (N = 1480). The new normative data indicate that the overall level of irritation in the German workforce is significantly lower compared to previously published data. Convergent and discriminant validity is confirmed by correlations with depression and anxiety (Patient Health Questionnaire-4 for Depression and Anxiety), somatic symptom scales (Bodily Distress Syndrome 25 checklist, Somatic Symptom Scale-8, Giessen Subjective Complaints List-8, comorbidity), psychological functioning (Mini-ICF rating for activity and participation disorders in mental illness), work-related stressors (overcommitment and bullying) and individual resources (self-efficacy). The results confirm the utility of the irritation scale and provide new benchmarks that avoid an underestimation of the levels of irritation in future studies.

Heart rate variability predicts outcome of short-term psychotherapy at the workplace.

The bio-psycho-social model highlights intra-individual and inter-individual interactions, including psychotherapy. The processing of these interactions within a person takes place, among others, in the central autonomic network (CAN). The CAN's autonomic output to the periphery can be indexed by heart rate variability (HRV), representing individual adaptive capacity. Further, the CAN influences the hypothalamus-pituitary-adrenal axis with its product cortisol. The aim consisted in investigating HRV and cortisol as well as their relation to symptom course in response to short-term psychotherapy. A single-arm, uncontrolled, explorative study was conducted at an outpatient psychotherapeutic consultation in the workplace offered to employees with mental or psychosomatic complaints. Questionnaires included symptoms of depression, irritation and functional impairment. Circadian profile of HRV and salivary cortisol concentrations collected pre and post short-term psychotherapeutic intervention (4-12 sessions) were assessed. Multilevel-linear mixed regressions were calculated. Out of 29 participants (mean age 42; 72% female), 24% were on sick leave from work. Cortisol concentrations were neither affected by intervention nor by symptom course. The proportion of individuals showing a vagally mediated HRV in the range of the lowest quartile assessed for age- and sex-matched healthy controls was reduced at follow-up (pre 34%, post 22%; p = .017). Higher vagally mediated HRV at baseline predicted lower symptom burden at follow-up. Thus, the results support the assumption that HRV reflects the capability of an organism to adapt and recover. Patients with reduced HRV might need additional psychotherapeutic sessions to achieve the same symptom improvements than patients with retained HRV.

Occupational physicians dealing with mental health: between employee and company interests: a qualitative study.

BACKGROUND: Occupational health physicians are increasingly confronted with mental health issues at their workplace. Facing them, most of them feel insecure and not sufficiently trained. Employee's mental well-being depends at the same time on individual and significantly on organizational variables. This complicates the physician's position, since they have to serve many interests. The focus of the present study is to investigate what difficulties occupational health physicians face and how organizational culture and management influence their work. METHODS: Interviews were conducted with N = 25 physicians as part of a training for basic mental health care. Interviews were interpreted using qualitative content analysis. RESULTS: Working with mentally ill employees was difficult for the physicians interviewed. Many felt insecure managing and preventing mental health issues. A need for further education was observed. Environmental factors (organizational culture, management) have a strong impact on the work of an occupational health physician and highlight its systemic dimension. Even though many of our participants report a meanwhile more open attitude towards mental disorders at their workplace, on the level of direct contact to the management prevail descriptions of little acceptance and a high priority of economic outcomes. CONCLUSIONS: More education on topics of mental health is needed for occupational health physicians. Future trainings should consider the intertwined nature of their work and enable them in dealing consciously with other actors in the company. For enhancing employee's mental well-being occupational health physicians could be granted a strengthened position in companies or be supported through more exchange with colleagues in other companies.

Conceptual Framework of a Psychotherapeutic Consultation in the Workplace: A Qualitative Study.

(1) Background: A new health care offer called 'psychotherapeutic consultation in the workplace' is an early and effective intervention for employees with common mental disorders. Although cost-effective, it lacks a broader roll-out. This might be attributable to undefined context, mechanisms of change, and a lack of communication; therefore, this study explores how the new model works and where problems occur. (2) Methods: Semi-structured interviews on motivation, expectations and experiences with 20 involved experts. Experts were members of the company health promotion team, service users, and cooperating mental health specialists. Analysis was conducted with ATLAS.ti. (3) Results: The conceptual framework comprises three main topics: (a) structured implementation concept; (b) persons involved, shaping the concept's processes; (c) and meaning and function of the offer within the given context. Concerning (c) we found three potential areas of conflict: (1) intra-corporate conflicts, (2) conflicts between company and employee, (3) and conflicts between the company health promotion and the health care system. Category (c) comprises the offer's core characteristics which were described as low-threshold and preventive. Furthermore, the offer was perceived as convenient in handling, confidential, and having immediate impact on a person's well-being. (4) Conclusions: Here we define structures, address the needs of the involved persons, and communicate foreseeable areas of conflict influences whether the implementation of the intervention succeeds.

Heart rate variability in the prediction of mortality: A systematic review and meta-analysis of healthy and patient populations.

Measures of heart rate variability (HRV) as a predictor of risk of disease and mortality have been investigated from various perspectives for more than six decades. The aim of the present comprehensive meta-analysis is to examine eight different HRV parameters to determine their association with all-cause and cardiac mortality. A total of 32 studies and two individual participant datasets (IPD) with 37 samples and 38,008 participants were included. Lower HRV parameter values were significant predictors of higher mortality across different ages, sex, continents, populations and recording lengths. Most of the examined parameters showed comparable hazard ratios (HR). IPD sub-analysis for heart rate corrected HRV parameters confirmed the strong association between HRV and all-cause mortality. Meta-regressions revealed no effect modifier for HRs extracted from covariate-adjusted studies. Sub-analyses of studies comparing the lowest quartile of 5-min root mean square of successive differences (RMSSD) vs. the other quartiles yielded a combined HR of 1.56 (95% CI: 1.32-1.85). The applicability of HRV measurement in preventive settings is discussed.

A randomized clinical trial to stimulate the cholinergic anti-inflammatory pathway in patients with moderate COVID-19-pneumonia using a slow-paced breathing technique.

Purpose: A characteristic problem occurring in COVID-19 is excessive elevations of pro-inflammatory cytokines (e.g. IL-6 and CRP) which are associated with worse clinical outcomes. Stimulation of the vagally-mediated cholinergic anti-inflammatory reflex by slow paced breathing with prolonged exhalation may present a clinically relevant way to reduce circulating IL-6. Method: Single-center randomized controlled clinical trial with enrolment of 46 patients hospitalized with confirmed severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (primary diagnosis). Differences between intervention (4sec inhalation, 6sec exhalation for 20 minutes 3x daily) and control group in IL-6 calculated using multilevel mixed-effect linear regression models with random slope including the covariates relevant comorbidities, COVID-19 medication, and age. Both groups received standard care. Results: Mean age was 57 years ± 13 years, N= 28 (60%) male, N=30 (65%) with relevant comorbidities. The model including group-by-time interaction revealed a significantly lower trajectory of IL-6 in the intervention group (effect size Cohens f2 = 0.11, LR-test p=.040) in the intention-to-treat sample, confirmed by per-protocol analysis (f2 = 0.15, LR-test p=.022). Exploratory analysis using the median split of practice time to predict IL-6 of the next morning indicated a dose-response relationship with beneficial effects of practice time above 45 minutes per day. Oxygen saturation remained unchanged during slow-paced breathing (95.1% ± 2.1% to 95.4% ± 1.6%). Conclusion: Patients practicing slow-paced breathing had significantly lower IL-6 values than controls with a small to medium effect size and without relevant side effects. Further trials should evaluate clinical outcomes and an earlier start of the intervention. Slow-paced breathing could be an easy to implement, low-cost, safe and feasible adjuvant therapeutic approach to reduce circulating IL-6 in moderate COVID-19 pneumonia. Clinical Trial Registration: https://www.drks.de, identifier DRKS00023971, Universal Trial Number (UTN) U1111-1263-8658.

A Single-Day Training for Managers Reduces Cognitive Stigma Regarding Mental Health Problems: A Randomized Trial.

BACKGROUND: Mental illnesses have received increasing attention in the work context in recent years, yet they are still often accompanied by stigma. One starting point for stigma reduction is interventions in the workplace. The present study evaluated a one-day workshop for managers in a large company. METHOD: Enrolled managers (n = 70) were randomly assigned to the intervention group and the waiting control group. The training included a theoretical section on mental and stress-related diseases as well as the interplay between work and health, group work on personal stress experience, theoretical input on dealing with mentally ill employees, and a group discussion on this topic along with case studies. Both groups completed the following questionnaires at baseline and three months after training: Effort-Reward Imbalance Questionnaire, Patient Health Questionnaire, Mental Health Knowledge Schedule, Social Distance Scale, and the Irritation Scale. RESULTS: Compared to the waiting group, the intervention group showed a significant improvement in the Mental Health Knowledge Schedule (U = 417.00, p = 0.040) and an increase in the Irritation Scale (U = 371.50 p = 0.011). All other scales remained unchanged. CONCLUSION: The content and duration of the training were adequate to reduce cognitive stigma towards mental illness. However, the present approach was not sufficient for an improvement in the subjective stress level of the participating managers.

Stress Management Intervention for Leaders Increases Nighttime SDANN: Results from a Randomized Controlled Trial.

Stress management interventions aim to reduce the disease risk that is heightened by work stress. Possible pathways of risk reduction include improvements in the autonomous nervous system, which is indexed by the measurement of heart rate variability (HRV). A randomized controlled trial on improving stress management skills at work was conducted to investigate the effects of intervention on HRV. A total of 174 lower management employees were randomized into either the waiting list control group (CG) or the intervention group (IG) receiving a 2-day stress management training program and another half-day booster after four and six months. In the trial, 24 h HRV was measured at baseline and after 12 months. Heart rate (HR), root mean square of successive differences (RMSSD), standard deviation of normal-to-normal intervals (SDNN), and standard deviation of the average of normal-to-normal intervals (SDANN) were calculated for 24 h and nighttime periods. Age-adjusted multilevel mixed effects linear regressions with unstructured covariance, time as a random coefficient, and time × group interaction with the according likelihood-ratio tests were calculated. The linear mixed-effect regression models showed neither group effects between IG and CG at baseline nor time effects between baseline and follow-up for SDANN (24 h), SDNN (24 h and nighttime), RMSSD (24 h and nighttime), and HR (24 h and nighttime). Nighttime SDANN significantly improved in the intervention group (z = 2.04, p = 0.041) compared to the control group. The objective stress axis measures (SDANN) showed successful stress reduction due to the training. Nighttime SDANN was strongly associated with minimum HR. Though the effects were small and only visible at night, it is highly remarkable that 3 days of intervention achieved a measurable effect considering that stress is only one of many factors that can influence HR and HRV.

Heightened Stress Reactivity in Response to an Attachment Related Stressor in Patients With Medically Treated Primary Hypertension.

Background: A heightened stress reactivity to mental stress tasks has been shown in hypertensive patients and might contribute to a higher disease risk. We investigated this hyperreactivity with regard to an attachment related stressor that focuses on emotions instead of performance and we examined whether this effect can also be found in patients on antihypertensive drugs. Materials and Methods: Fifty patients with primary hypertension, treated with at least one antihypertensive drug, were compared with 25 healthy individuals. After 10 min of rest, they participated in an attachment-related interview (Adult Attachment Projective picture system, AAP) and were exposed to an attachment-related stressor (Separation Recall, SR), a short-time stressor which activates attachment-related emotions and thoughts by talking 5 min about a personal experience of loneliness. Blood samples to measure adrenocorticotrope hormone (ACTH), cortisol, norepinephrine, epinephrine, and dopamine were taken. Blood pressure, heart rate and arterial stiffness were measured at rest, after AAP, after SR and 10 min after recovery. Standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD) were calculated. Parameters were compared using Mann Whitney U-test and linear mixed-effects regression models controlling for age and body mass index (BMI) after logarithmic transformation if appropriate. Results: Healthy test persons were younger and had lower BMI than patients. Comparing the two groups there were no significant differences in blood pressure and heart rate at rest. Both stressors provoked a significant response in almost all parameters. Results of the post-estimation of contrasts from linear mixed-effects regression models showed a steeper rise in systolic BP and arterial stiffness as well as a more pronounced decline in SDNN in hypertensive patients than in healthy controls. Levels of cortisol rose earlier and higher in hypertensive patients than in healthy controls. Conclusion: Vascular, autonomic, and hypothalamic pituitary adrenal axis response is heightened in medicated subjects with hypertension in response to attachment-focused stressors compared to healthy subjects. We conclude that the remaining hyper-reactivity even with sufficient antihypertensive medication still poses a substantial risk for affected patients. New ways to diminish this risk should be developed.

[Providing Rapid Help for Mental Strain at the Workplace: Psychosomatic Consultation in the Workplace]. / Rasche Hilfe bei psychischen Belastungen am Arbeitsplatz: Die Psychosomatische Sprechstunde im Betrieb.

BACKGROUND: Psychosomatic consultation in the workplace (PSIW) is an offer for employees who are under mental and psychosomatic strain. Core elements are early diagnosis and short-term psychotherapy with the aim of improving the care for mentally stressed employees. This article provides a characterization of patients and presents initial data on the effects of short-term psychotherapy. MATERIALS AND METHODS: From 05/2016 to 12/2019, basic data were collected from all employees seeking help. Socio-demographic data, previous treatments, work ability, depression (PHQ-9), anxiety (GAD-7), somatic symptoms (PHQ-15), assessment of psychological state and attitudes towards treatment options were collected by self-report before and (if applicable) after a short-term intervention. RESULTS: A total of 672 employees from 20 companies (49% male) were mostly referred to PSIW by the company physician. Adjustment disorders and depressive disorders each accounted for almost one-third of diagnoses. A quarter of the employees presenting at PSIW were on sick leave at the time of referral. The most frequent recommendations were short-term intervention at PSIW, followed by outpatient psychotherapy. A total of 343 (51%) employees completed the questionnaires, of which 187 (55%) of them received short-term psychotherapy. The symptoms improved significantly across all scales. Satisfaction with PSIW was very high. CONCLUSIONS: PSIW is an innovative care concept in the work context, which is well accepted and effective in various sectors. Close cooperation with company stakeholders such as occupational health physicians is important for a successful outcome.

24 h-Heart Rate Variability as a Communication Tool for a Personalized Psychosomatic Consultation in Occupational Health.

New tools for non-specific primary prevention strategies covering somatic and mental health in occupational medicine are urgently needed. Heart rate variability (HRV) reflects the capacity of the body to adapt to environmental challenges and of the mind to regulate emotions. Hence, a 24 h-measurement of HRV offers a unique possibility to quantify the interaction between situation-specific emotional regulation within a specific psychosocial environment and physiological state, thereby increasing self-perception and inducing motivation to change behavior. The focus of the present study represents such a 24 h-measurement of HRV and its presentation as a comprehensive graph including protocol situations of the client. A special training program for occupational health physicians and questionnaires for clients were developed and administered. The article reports the first data of the study "healthy leadership and work - body signals for managers and employees", an investigator-initiated, interventional, single-arm, open (non-blinded), multicenter, national trial with 168 participants. They reported a significantly improved perception of their bodily needs after the consultation (from Median = 7, interquartile range 5-8 to Median = 8, interquartile range 7-9; scale range from 1 to 10; p < 0.001, Wilcoxon rank test; effect size 0.49). The 16 occupational health physicians stated that the measurement of HRV was very well suited to enter into dialog with the managers and was feasible to show interactions between situations, thoughts, feelings, and bodily reactions. Taken together, we show that a 24 h-HRV-measurement can be a feasible and effective approach for holistic, psychosomatic primary prevention in occupational medicine. We discuss possible mechanisms for improving the individual health via the consultation, containing mindset and improved ANS activity.

Psychische Erkrankungen im Arbeitskontext ­ eine Verortung im Versorgungssystem.

Work and mental health are closely interrelated. Sick leave rates due to mental illness have constantly been rising for years. Thus, not only companies but also the society as a whole have become more and more aware of the relevance of this topic.At first, various work stress models are outlined in this article. This is followed by an overview of how to classify work-related mental disorders in the ICD and DSM systems. Burnout is explained with regard to terminology, origin and adequate use in clinical practice. Furthermore, the ILO (International Labour Organization) classification of work-related mental disorders is presented. Possible intervention models for the prevention and therapy of work-related mental health problems are discussed. In addition, the most essential components of work-related psychotherapy are pointed out. Finally, corresponding guidelines are put into an international context.

Who Should Play a Key Role in Preventing Common Mental Disorders that Affect Employees in the Workplace? Results of a Survey with Occupational Health Physicians, Primary Care Physicians, Psychotherapists, and Human Resource Managers.

The rising burden of common mental disorders (CMDs) in employees requires strategies for prevention. No systematic data exist about how those involved perceive their roles, responsibilities, and interactions with other professional groups. Therefore, we performed a multi-professional standardized survey with health professionals in Germany. A self-administered questionnaire was completed by 133 occupational health physicians (OHPs), 136 primary care physicians (PCPs), 186 psychotherapists (PTs), and 172 human resource managers (HRMs). Inter alia, they were asked which health professionals working in the company health service and in the outpatient care or in the sector of statutory insurance agents should play a key role in the primary, secondary, and tertiary prevention of CMDs in employees. The McNemar test was used in order to compare the attributed roles among the professionals involved. With regard to CMDs, all the professional groups involved in this study declared OHPs as the most relevant pillar in the field of prevention. In primary prevention, HRMs regarded themselves, OHPs, and health insurance agents as equally relevant in terms of prevention. PTs indicated an important role for employee representatives in this field. In secondary prevention, PCPs were regarded as important as OHPs. HRMs indicated themselves as equally important as OHPs and PCPs. In tertiary prevention, only OHPs identified themselves as main protagonists. The other groups marked a variety of several professions. There is a common acceptance from the parties involved that might help the first steps be taken toward overcoming barriers, e.g., by developing a common framework for quality-assured intersectional cooperation in the field of CMD prevention in employees.

[How do users assess the new "Psychosomatic Consultation in the Workplace" model of care? : Results of a controlled observational trial]. / Wie bewerten Nutzer das neue Versorgungsmodell "Die Psychosomatische Sprechstunde im Betrieb"? : Ergebnisse einer kontrollierten Beobachtungsstudie.

BACKGROUND: Within the framework of psychosomatic consultation in the workplace (PSIW), external expert psychotherapists offered consultation sessions for employees at the company premises in order to establish a first contact. In contrast to the first contact usually established in regular care, PSIW explicitly focuses on the workplace and enables in-company actors to get closely involved, if the patient's consent is provided. The new model of care helps to identify mental problems at an early stage and is clinically effective. Reliable data considering the user's point of view is missing. OBJECTIVES: How satisfied are users of the new model of care compared to users of regular care? MATERIAL AND METHODS: A total of 189 people from in-company (n = 91) or regular medical consultations (n = 98) made statements before first contact (t1) and 12 weeks (t2) after the initial contact. They reported satisfaction with the offer (t2), further treatment (t2), and depressiveness (t1, t2) by means of self-assessment tools. On the basis of an OLS (ordinary least squares) regression analysis, we investigated how treatment quality (clinical improvement, further treatment) and the place of treatment influenced user satisfaction (dependent variable), while controlling for selection bias and the different degrees of depression at baseline. RESULTS: Higher clinical improvement predicted more satisfaction with the received treatment in both (b = 1.2, CI 0.802-1.548). The mean value (MV) of satisfaction was 1.6 points higher if further treatment took place (CI 0.236-2.909). PSIW users showed a 1.8 points higher MV of satisfaction than people in regular care (CI 0.322-3.302). CONCLUSIONS: PSIW users consider PSIW as positive in terms of treatment success and service quality.

Prevention of Common Mental Disorders in Employees. Perspectives on Collaboration from Three Health Care Professions.

Collaboration among occupational health physicians, primary care physicians and psychotherapists in the prevention and treatment of common mental disorders in employees has been scarcely researched. To identify potential for improvement, these professions were surveyed in Baden-Württemberg (Germany). Four hundred and fifty occupational health physicians, 1000 primary care physicians and 700 resident medical and psychological psychotherapists received a standardized questionnaire about their experiences, attitudes and wishes regarding activities for primary, secondary and tertiary prevention of common mental disorders in employees. The response rate of the questionnaire was 30% (n = 133) among occupational health physicians, 14% (n = 136) among primary care physicians and 27% (n = 186) among psychotherapists. Forty percent of primary care physicians and 33% of psychotherapists had never had contact with an occupational health physician. Psychotherapists indicated more frequent contact with primary care physicians than vice versa (73% and 49%, respectively). Better cooperation and profession-specific training on mental disorders and better knowledge about work-related stress were endorsed. For potentially involved stakeholders, the importance of interdisciplinary collaboration for better prevention and care of employees with common mental disorders is very high. Nevertheless, there is only little collaboration in practice. To establish quality-assured cooperation structures in practice, participants need applicable frameworks on an organizational and legal level.

High Prevalence of Insecure Attachment in Patients with Primary Hypertension.

Hypertension is a major cardiovascular (CV) risk factor and is predicted by heightened CV reactivity to stress in healthy individuals. Patients with hypertension also show an altered stress response, while insecure attachment is linked to a heightened stress reactivity as well. This is the first study aiming to assess attachment representations in patients with primary hypertension and to investigate their CV responses when their attachment system is activated. We studied 50 patients (38 men, 12 women) with primary hypertension. The Adult Attachment Projective Picture System (AAP), a widely used and validated interview, was performed to measure the patients' attachment representations, and to activate their attachment system. Blood pressure and heart rate were measured after 10 min at rest prior to and directly after the AAP interview. Mood and state anxiety were assessed using the Multidimensional Mood State Questionnaire (MDBF) and the State Trait Anxiety Inventory-State (STAI-S) before and after the experiment. The prevalence of insecure attachment (dismissing, preoccupied, unresolved) in hypertensive patients was predominant (88%), while in non-clinical populations, only about 50% of individuals had insecure attachment patterns. Blood pressure (p < 0.001), heart rate (p = 0.016), and rate pressure product (p < 0.001) significantly increased in response to the attachment interview. Secure attached patients showed the highest rise in systolic blood pressure (p = 0.020) and the lowest heart rate compared to the other attachment groups (p = 0.043). However, attachment representation showed no significant group or interaction effects on diastolic blood pressure (DBP) and rate pressure product. Insecure attachment was highly over-represented in our sample of patients with primary hypertension. Additionally, a robust CV response to the attachment-activating stimulus was observed. Our data suggest that insecure attachment is significantly linked to primary hypertension, which implies the need for further investigations to evaluate attachment insecurity as a possible risk factor for hypertension.

High prevalence of posttraumatic stress in patients with primary hypertension.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with a higher rate of arterial hypertension. However, data about prevalence rates of PTSD in patients suffering from arterial hypertension as well as the relation to blood pressure (BP) control are lacking. METHODS: We recruited 145 patients with primary hypertension from March to November 2012 at the cardiologic outpatient clinic at Ulm University Medical Center. Symptoms of PTSD (assessed with the Posttraumatic Diagnostic Scale), perceived stress (Perceived Stress Scale; Trier Inventory for Chronic Stress), depression and anxiety (Hospital Anxiety and Depression Scale) were assessed by self-report. Office BP was measured and medical data were collected. RESULTS: Criteria for a full PTSD syndrome were met by 13 patients (9%). Posttraumatic stress was higher in the group of patients with controlled (M=10.9, S.D.=9.8) than in those with uncontrolled hypertension (M=3.9, S.D.=5.4; P<.001). In linear regression, only status of hypertension control (beta=.39, P<.001) predicted posttraumatic stress significantly, even after controlling for important cofactors. CONCLUSIONS: PTSD is highly prevalent in hypertensive patients, especially in those with controlled hypertension. An explaining mechanism could be the higher use of health care by patients suffering from PTSD. The mental needs of these patients should be focused in addition to the well-established somatic care.

Opposite effects of serotonin and interferon-alpha on the membrane potential and function of human natural killer cells.

In an earlier article, we reported that serotonin (5-hydroxytryptamine, 5-HT) inhibits the natural killer cell (NK) cytotoxicity of human whole blood in a dose-dependent manner and that natural human interferon-alpha (IFN-alpha) partially eliminates this effect. Because natural IFN-alpha might contain factors other than IFN, we repeated these experiments with recombinant human interferon-alpha (rhIFN-alpha) and separated blood lymphocytes enriched with NK cells and then demonstrated that IFN really is responsible for this effect. Furthermore, this investigation was carried out to clarify the mechanisms of the action of 5-HT and of rhIFN-alpha on NK cells. The inhibition of the cytotoxicity was pronounced when 5-HT was added at the onset of the cytotoxic assay, whereas the pretreatment of lymphocytes for 18 h only led to a slight inhibition. Moreover, rhIFN-alpha applied 1 h before or 1 h after the addition of 5-HT decreased the inhibitory effect of 5-HT. Flow cytometric analysis involving the use of a voltage-sensitive dye, oxonol, revealed that 5-HT depolarized, whereas rhIFN-alpha hyperpolarized the plasma membrane of the lymphocytes. Thus, it seems likely that the inhibitory effect of 5-HT on the cytotoxicity of peripheral human lymphocytes is due to the depolarization on the plasma membrane of the effector cells and that rhIFN-alpha antagonizes this ability via its hyperpolarizing activity.

Cross-reactivity between human adenoviruses in delayed-type hypersensitivity.

The aim of this study was to determine the antigen responsible for the induction of delayed-type hypersensitivity (DTH) by human adenoviruses (Ads). The estimation of DTH was based on measurement of the extent of swelling of the hind footpads of mice. CsCl density gradient-purified human Ad serotype 6 (Ad6) induced DTH in a dose-dependent manner. In Ad6-sensitized mice, DTH could be elicited by serotypes belonging to the same species of human Ads (types 1 and 5) and by a serotype (type 3) belonging to another species. Latex particles coated with purified hexon antigen prepared from Ad5 had the capacity to sensitize mice and elicit a DTH reaction. We suggest that, for serotypes belonging to species C, the cross-reactive highly conserved T cell epitope of the hexon protein might be responsible for the DTH induction, and furthermore the same epitope might result in the cross-reactivity between serotypes 3 and 6. The possible importance of these data is discussed in relation to human gene therapy through the application of Ad vectors.