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Biomedical subjects

Ulrike Ehlert

Publications and source records attributed to Ulrike Ehlert.

At least 19 recordsLinked to original sources

Salivary alpha-amylase levels after yohimbine challenge in healthy men.

CONTEXT: We and others have previously shown that standardized psychosocial stress significantly increases salivary alpha-amylase (sAA), but it remains unclear whether sAA reflects autonomic nervous system activation. OBJECTIVE: The aim of this study was to assess cardiovascular effects and sAA and catecholamine secretion after iv injection of yohimbine. DESIGN AND SETTING: We conducted a randomized double-blind placebo-controlled study at an academic research unit. PARTICIPANTS: Thirteen healthy males (aged 20-28 yr) were examined. INTERVENTION: Participants received iv injection of yohimbine (0.4 microg/kg) or placebo (0.9% NaCl). MAIN OUTCOME MEASURES: Eight saliva and blood samples were taken before and after injection for the assessment of salivary flow rate and sAA and catecholamine concentrations. In addition, blood pressure, mood, and anxiety were assessed repeatedly. RESULTS: Yohimbine induced increases of sAA activity and output in comparison to placebo (P = 0.034). Blood pressure (P < 0.001), salivary flow rate (P = 0.007), and catecholamines (P < 0.001) were also significantly increased. No significant correlations between alpha-amylase parameters and catecholamines were observed. CONCLUSIONS: The results indicate that yohimbine administration activates not only autonomic parameters but also sAA via adrenergic mechanisms, suggesting that sAA might be an indirect indicator of the central sympathetic system.

Adrenergic alpha-Antagonists↗

Onset and maintenance of psychiatric disorders after serious accidents.

The purpose of this study was to prospectively investigate the onset, course, and remission of psychiatric disorders in the first 6 months after a serious accident for consecutive patients in a hospital emergency department. Participants were 58 patients aged 18-65 who were assessed shortly after attending a hospital emergency department and were followed up 6 months afterwards. Patients were interviewed with regard to past and current psychiatric history using different instruments (e.g. SCID for DSM-IV). Prior to their accidents, 35% of all subjects had experienced one or more psychiatric disorders (lifetime prevalence). Shortly after the accident, the incidence of Acute Stress Disorder (7%), subsyndromal Acute Stress Disorder (12%), and adjustment disorder (1.5%) was increased as a reaction to the accident. At this time, 29% of all patients suffered from an acute psychiatric disorder. Six-months after the accident, 10% of the subjects met criteria for Major Depression, 6% for PTSD, 4% for subsyndromal PTSD, and 1.5% for Specific Phobia as newly developed disorders. The course of the psychiatric disorders shows that those patients who met criteria for any psychiatric diagnosis shortly after the accident ran a much higher risk for developing new or comorbid psychiatric disorders in the future.

Abbreviated Injury Scale↗

Low social support and poor emotional regulation are associated with increased stress hormone reactivity to mental stress in systemic hypertension.

CONTEXT: There is strong evidence for a physiological hyperreactivity to stress in systemic hypertension, but data on associated or potentially moderating psychological factors are scarce. OBJECTIVE: The objective of the study was to identify psychological correlates of physiological stress reactivity in systemic hypertension. DESIGN: This was a cross-sectional, quasi-experimentally controlled study. Study participants underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. SETTING: The study was conducted in the population in the state of Zurich, Switzerland. SUBJECTS: Subjects included 22 hypertensive and 26 normotensive men (mean +/- sem 44 +/- 2 yr). MAIN OUTCOME MEASURES: We assessed the psychological measures social support, emotional regulation, and cognitive appraisal of the stressful situation. Moreover, we measured salivary cortisol and plasma epinephrine and norepinephrine before and after stress and several times up to 60 min thereafter as well as blood pressure and heart rate. RESULTS: We found poorer hedonistic emotional regulation (HER) and lower perceived social support in hypertensives, compared with normotensives (P < 0.01). Compared with normotensives, hypertensives showed higher cortisol, epinephrine, and norepinephrine secretions after stress (P < 0.038) as well as higher systolic and diastolic blood pressure (P < 0.001). Cortisol reactivity and norepinephrine secretion were highest in hypertensive men with low HER (P < 0.05). In contrast, hypertensives with high HER did not significantly differ from normotensives in both cortisol and norepinephrine secretion after stress. Epinephrine secretion was highest in hypertensives with low social support but was not different between hypertensives with high social support and normotensives. CONCLUSIONS: The findings suggest that both low social support and low HER are associated with elevated stress hormone reactivity in systemic hypertension.

Adult↗

Sex differences in emotional and psychophysiological responses to musical stimuli.

Although it is known that men and women differ in their music preferences and emotional reactions to music, little is known about sex differences in physiological reactions to music. In our study, we therefore set out to examine the differential reactivity to two musical stimuli that elicit distinct psychological and physiological reaction patterns. Fifty-three healthy subjects (mean age: 26.13, SD: 3.97; 26 males, 27 females) were examined. Heart rate, electrodermal activity, skin temperature, salivary cortisol, salivary alpha-amylase, and psychological variables were assessed during the course of the whole study. Following baseline assessment, two musical stimuli, which were carefully selected and rated in a pre-study as relaxing and pleasant (renaissance music) and arousing and unpleasant (heavy metal), respectively, were introduced. They were presented on two different days in a randomized order. Whereas psychological variables did not differ between men and women, results of electrophysiological measures indicate significantly different reactivity patterns between men and women. Women displayed elevated response curves to the arousing and unpleasant stimulus, whereas men did not. However, no differences were found with regards to endocrine measures in saliva. Our results demonstrate sex differences in reactivity patterns to musical stimuli in psychophysiological measures. In our study, we were able to show that women tend to show hypersensitivity to aversive musical stimuli. This finding is in accordance with previous literature on sex differences in emotion research. Furthermore, our study indicates that the confounding effects of sex differences have to be considered when using musical stimuli for emotion induction.

Acoustic Stimulation↗

Psychosocial stress enhances time-based prospective memory in healthy young men.

Forgetting of intentions (such as to take one's medication) is the most frequent everyday memory failure. No study so far has looked into the possible consequences stress might exert on memory for intentions (i.e., prospective memory). Twenty healthy young male adults were exposed to a psychosocial stress test and a non-stress condition. After a delay of 15 min, a time- and an event-based prospective memory task were administered during the peak of cortisol concentrations. Results show that participants performed significantly better in the time-based memory task after stress in comparison to the non-stress condition. In contrast, there was no stress effect on event-based prospective memory. The results demonstrate that prospective memory might be enhanced when participants are exposed to stress prior to the memory task and that this effect is associated to stress-related glucocorticoid effects.

Adult↗

Glucocorticoids reduce phobic fear in humans.

Phobias are characterized by excessive fear, cued by the presence or anticipation of a fearful situation. Whereas it is well established that glucocorticoids are released in fearful situations, it is not known whether these hormones, in turn, modulate perceived fear. As extensive evidence indicates that elevated glucocorticoid levels impair the retrieval of emotionally arousing information, they might also inhibit retrieval of fear memory associated with phobia and, thereby, reduce phobic fear. Here, we investigated whether acutely administrated glucocorticoids reduced phobic fear in two double-blind, placebo-controlled studies in 40 subjects with social phobia and 20 subjects with spider phobia. In the social phobia study, cortisone (25 mg) administered orally 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation, exposure, and recovery phase of the stressor. Moreover, the stress-induced release of cortisol in placebo-treated subjects correlated negatively with fear ratings, suggesting that endogenously released cortisol in the context of a phobic situation buffers fear symptoms. In the spider phobia study, repeated oral administration of cortisol (10 mg), but not placebo, 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again 2 days after the last cortisol administration, suggesting that cortisol may also have facilitated the extinction of phobic fear. Cortisol treatment did not reduce general, phobia-unrelated anxiety. In conclusion, the present findings in two distinct types of phobias indicate that glucocorticoid administration reduces phobic fear.

Animals↗

Prolonged salivary cortisol recovery in second-trimester pregnant women and attenuated salivary alpha-amylase responses to psychosocial stress in human pregnancy.

CONTEXT: The underlying biological mechanisms of stress-related pregnancy complications in humans are still poorly understood. Recent research on pharmacological or physical provocation procedures in pregnant women has resulted in inhomogeneous findings. Furthermore, no studies conducted so far have used a psychosocial stress paradigm at different stages of pregnancy. OBJECTIVE: The aim of this study was to identify endocrine, autonomic, and psychological responses to standardized psychosocial stress at different stages of pregnancy. DESIGN: Ninety healthy women (aged 21-37 yr), including 30 pregnant women at the beginning of the second trimester and 30 women at the beginning of the third trimester, as well as 30 nonpregnant women in the follicular phase of their menstrual cycle, underwent a psychosocial stress test. Salivary free cortisol, alpha-amylase, heart rate, and psychological parameters were repeatedly measured. RESULTS: Salivary cortisol recovery was significantly prolonged in second-trimester pregnant women (P = 0.04). Cortisol and heart rate increases of both pregnant groups were shown to be comparable with those of the controls. alpha-Amylase increases of both pregnant groups were markedly attenuated compared with nonpregnant women (P = 0.008). CONCLUSIONS: From these data, we conclude that, in contrast to pregnancy in rats, pregnancy in women does not result in a restraint of the hypothalamic-pituitary-adrenal axis to psychosocial stress. Furthermore, attenuated alpha-amylase stress response might reflect protective processes within the autonomic nervous system during pregnancy, whereas prolonged cortisol recovery during the beginning of second-trimester pregnancy might be associated with the vulnerability to stress-related pregnancy complications during this period of time.

Adult↗

Emotional well-being and predictors of birth-anxiety, self-efficacy, and psychosocial adaptation in healthy pregnant women.

BACKGROUND: A broad body of studies have shown that emotional well-being during pregnancy influences birth outcome and postpartum mood state, but few longitudinal studies have examined the extent of changes of emotional well-being during late pregnancy. Furthermore, up to now it has remained unclear which factors are predictive for emotional well-being during pregnancy. This prospective longitudinal study has two main aims. First of all, possibly occurring changes of birth anxiety, self-efficacy for labor and delivery, and psychosocial adaptation to pregnancy in primiparous healthy women during the final trimenon will be described. Second, predictors of these assessed constructs during the final trimenon as well as the extent of these constructs as predictors for the psychological status postpartum will be shown. METHODS: A prospective longitudinal study was conducted with 61 pregnant women recruited from childbirth classes. RESULTS: The results showed significant changes in emotional well-being--measured by birth anxiety, self-efficacy for labor and delivery, and psychosocial adaptation to pregnancy--during the final trimenon: the women were more confident in their ability to cope with labor and delivery. Birth anxiety did not change significantly during the final trimenon. Regression analyses revealed different psychosocial predictor variables for emotional well-being during late pregnancy. The predictive factor for an unfavorable psychological status postpartum was birth anxiety. CONCLUSIONS: The results of this study suggest that the importance of discovering psychosocial problems of pregnant woman early in pregnancy could be imperative in preventing psychosocial problems later in pregnancy as well as postpartum.

Adaptation, Psychological↗

Recent trends in behavioral medicine.

PURPOSE OF REVIEW: Behavioral medicine is an interdisciplinary field, integrating research from a variety of disciplines. This review focuses on recent advances and developments in behavioral medicine. RECENT FINDINGS: Stress, as well as having a role in the etiology and maintenance of somatic disease and somatoform disorders, is an important factor in the behavioral medicine literature. Consequentially, recent advances in psychological interventions targeting these conditions were developed. Furthermore, a variety of psychobiological mechanistic studies investigating the dysregulations of stress axes in conditions relevant to behavioral medicine have been undertaken. SUMMARY: Studies investigating factors and processes relevant to health and illness clearly demonstrate the impact of psychosocial factors such as stress. The biopsychosocial perspective becomes increasingly sophisticated, focusing on specific disease processes and empirically tested and effective interventions.

Behavioral Medicine↗

The role of stress hormones in the relationship between resting blood pressure and coagulation activity.

BACKGROUND: Systemic hypertension confers a hypercoagulable state. We hypothesized that resting mean blood pressure (MBP) interacts with stress hormones in predicting coagulation activity at rest and with acute mental stress. METHODS: We measured plasma clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, epinephrine and norepinephrine, and saliva cortisol in 42 otherwise healthy normotensive and hypertensive medication-free men (mean age 43 +/- 14 years) at rest, immediately after stress, and twice during 60 min of recovery from stress. RESULTS: At rest, the MBP-by-epinephrine interaction predicted FVII:C (beta = -0.33, P < 0.04) and D-dimer (beta = 0.26, P < 0.05), and the MBP-by-cortisol interaction predicted D-dimer (beta = 0.43, P = 0.001), all independent of age and body mass index (BMI). Resting norepinephrine predicted fibrinogen (beta = 0.42, P < 0.01) and D-dimer (beta = 0.37, P < 0.03), both independent of MBP. MBP predicted FVIII:C change from rest to immediately post-stress independent of epinephrine (beta = -0.37, P < 0.03) and norepinephrine (beta = -0.38, P < 0.02). Cortisol change predicted FVIII:C change (beta = -0.30, P < 0.05) independent of age, BMI and MBP. Integrated norepinephrine change from rest to recovery (area under the curve, AUC) predicted D-dimer AUC (beta = 0.34, P = 0.04) independent of MBP. The MBP-by-epinephrine AUC interaction predicted FVII:C AUC (beta = 0.28) and fibrinogen AUC (beta = -0.30), and the MBP-by-norepinephrine AUC interaction predicted FVIII:C AUC (beta = -0.28), all with borderline significance (Ps < 0.09) and independent of age and BMI. CONCLUSIONS: MBP significantly altered the association between stress hormones and coagulation activity at rest and, with borderline significance, across the entire stress and recovery interval. Independent of MBP, catecholamines were associated with procoagulant effects and cortisol reactivity dampened the acute procoagulant stress response.

Adult↗

Reduced reactivity and enhanced negative feedback sensitivity of the hypothalamus-pituitary-adrenal axis in chronic whiplash-associated disorder.

Dysregulations of the hypothalamus-pituitary-adrenal (HPA) axis have been discussed as a physiological substrate of chronic pain and fatigue. The aim of the study was to investigate possible dysregulations of the HPA axis in chronic whiplash-associated disorder (WAD). In 20 patients with chronic WAD and 20 healthy controls, awakening cortisol responses as well as a short circadian free cortisol profile were assessed before and after administration of 0.5mg dexamethasone. In comparison to the controls, chronic WAD patients had attenuated cortisol responses to awakening, normal cortisol levels during the day, and showed enhanced and prolonged suppression of cortisol after the administration of 0.5mg dexamethasone. Dysregulations of the HPA axis in terms of reduced reactivity and enhanced negative feedback suppression exist in chronic WAD. The observed endocrine abnormalities could serve as a systemic mechanism of symptoms experienced by chronic WAD patients.

Adult↗

Stress-induced changes in human salivary alpha-amylase activity -- associations with adrenergic activity.

The salivary enzyme alpha-amylase has been proposed to indicate stress-reactive bodily changes. A previous study by the authors revealed marked increases in salivary alpha-amylase following psychosocial stress, indicating a stress-dependent activation of salivary alpha-amylase. Salivary alpha-amylase has been suggested to reflect catecholaminergic reactivity. Our aim was to assess/evaluate a possible relationship between salivary alpha-amylase and adrenergic parameters, i.e. catecholamines, as well as other stress markers. Using an intra-individual repeated measures design, 30 healthy young men underwent the Trier Social Stress Test (TSST), which consists of a mental arithmetic task and free speech in front of an audience and a control condition in randomized order. Salivary alpha-amylase and salivary cortisol as well as plasma catecholamines and cardiovascular activity were repeatedly measured before, during, and after both conditions. Significant differences were found between the stress and the rest condition in salivary alpha-amylase, salivary cortisol, plasma catecholamines, and cardiovascular parameters (heart rate, LF, HF, LF/HF). However, general alpha-amylase responses (area under the curve) were not associated with general responses in catecholamines and cortisol in the stress condition (r smaller than 0.25 for all analyses). Analysis of cardiovascular parameters indicates a positive relationship between amylase and sympathetic tone (LF/HF) during stress. Salivary alpha-amylase is sensitive to psychosocial stress. Since it does not seem to be closely related to other biological stress markers such as catecholamines and cortisol, salivary alpha-amylase may be a useful additional parameter for the measurement of stress.

Adult↗

Human salivary alpha-amylase reactivity in a psychosocial stress paradigm.

Biological indicators for stress reactions are valuable markers in psychophysiological research and clinical practice. Since the release of salivary enzyme alpha-amylase was reported to react to physiological and psychological stressors, we set out to investigate human salivary alpha-amylase changes employing a reliable laboratory stress protocol to investigate the reactivity of salivary alpha-amylase to a brief period of psychosocial stress. In a within-subject repeated-measures design, 24 healthy adults were exposed to the TSST and a control condition on separate days with randomized sequence. Salivary alpha-amylase, salivary cortisol and heart rate were repeatedly measured before, during and after both conditions. Significant differences between psychosocial stress and the rest condition in alpha-amylase activity [F(3.74,86.06)=4.52; P=0.003], cortisol levels [F(4.21,88.32)=12.48; P<0.001] and heart rate [F(1,22)=81.15; P<0.001] were observed, with marked increases before and after stress. The data corroborate findings from other studies that showed increased levels of alpha-amylase before and after psychological stress. We discuss the role of salivary alpha-amylase as a promising candidate for a reliable, noninvasive marker of psychosocial stress.

Adult↗

High and low unstimulated salivary cortisol levels correspond to different symptoms of functional gastrointestinal disorders.

OBJECTIVE: It was examined whether unstimulated salivary cortisol levels as a psychobiological marker of stress reactivity correspond to psychological assessments of pain perception, depressive mood, and anxiety in patients with functional gastrointestinal disorder (FGD). METHODS: A total of 30 patients was diagnosed according to the Rome diagnostic criteria for irritable bowel syndrome, nonulcer dyspepsia, or both conditions. Psychometric data were assessed by questionnaires, and salivary samples were collected for the measurement of cortisol levels after awakening and during the day. Patients were grouped by their awakening cortisol levels into low (G1), medium (G2), and high cortisol group (G3). RESULTS: Psychiatric comorbidity did not differ between the groups. Analysis of variance (ANOVA) showed significant group differences with respect to pain perception and depressive mood, with the highest pain in G1 and the highest depression in G3. CONCLUSION: The reported results are in line with prior research on hypothalamus-pituitary-adrenal (HPA) axis dysregulation in patients suffering from somatoform disorders on the one hand (low cortisol levels) and high cortisol levels in depression on the other. It is remarkable that our sample of patients of whom all received the same diagnosis, i.e., FGD, can be subdivided according to functional gastrointestinal symptoms, which correspond to the two types of cortisol alterations. The data provide evidence for psychobiological subgroups in FGD patients. As a consequence, the predominant symptoms reported by patients with FGD should carefully be taken into account to specify (psychotherapeutic) treatment.

Adult↗

Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome.

OBJECTIVE: It has been suggested that a hypofunctional hypothalamic-pituitary-adrenal (HPA) axis in chronic fatigue syndrome could result in an exaggerated release of pro-inflammatory cytokines during stress. As pro-inflammatory cytokines are involved in the induction of sickness behavior and thus constitute a potential physiological correlate of stress-induced symptom exacerbation in chronic fatigue syndrome, we set out to evaluate the LPS-induced production of pro-inflammatory cytokines during psychosocial stress in CFS and healthy controls. METHOD: Twenty-one CFS patients and 20 healthy controls matched for age and gender underwent a standardized psychosocial stress test (Trier social stress test, TSST). Adrenocorticotropine hormone (ACTH), salivary cortisol and plasma cortisol levels were measured before and repeatedly following exposure to the stressor. Lipopolysaccharide-stimulated production of interleukin-6 and tumor necrosis factor-alpha were assessed at baseline as well as 10 and 60 min after the stress test. RESULTS: CFS patients showed an inverse stress-induced response pattern of LPS-stimulated cytokines responses in comparison to healthy controls, i.e. stimulated cytokine production decreased shortly after stress in CFS patients, while it increased in controls. Fatigue scores and basal LPS-induced cytokine levels were significantly associated for TNF-alpha in controls and for both cytokines in CFS patients. Stress-induced changes in stimulated cytokine production were not associated with general fatigue scores in the control group, whereas in the CFS group, fatigue scores were significantly correlated with integrated levels of LPS-induced cytokines. However, partial correlations revealed that these results were due to the high correlations with basal LPS-induced cytokine levels. CONCLUSION: CFS patients do not show an exaggerated secretion of LPS-induced cytokines. Although cortisol responses to stress were normal, pro-inflammatory cytokine levels in CFS patients were significantly attenuated. Possible intracellular mechanisms, such as for example an enhanced sensitivity to inhibitory effects of glucocorticoids, a diminished responsivity to catecholaminergic stimulation, and a disruption of intracellular activation are discussed. Basal levels of stimulated pro-inflammatory Il-6 levels are generally related to fatigue scores. However, in CFS patients this association is of greater magnitude and can also be observed for TNF-alpha.

Adrenocorticotropic Hormone↗

Predicting posttraumatic stress symptoms from pretraumatic risk factors: a 2-year prospective follow-up study in firefighters.

OBJECTIVE: Most studies focusing on risk factors for posttraumatic stress disorder (PTSD) have used retrospective study designs. Only a small number of studies have prospectively examined risk factors in the immediate aftermath of trauma exposure in predicting PTSD symptoms. The purpose of this study was to identify predictive risk factors for posttraumatic stress symptoms and comorbid psychopathological symptoms present during the time before exposure to traumatic stress in a high-risk population. METHOD: Forty-three professional firefighters were assessed immediately after basic training (baseline) and at 6, 9, 12, and 24 months after entry into firefighter service. Subjects were screened for psychopathological symptoms, including symptoms of PTSD, depression, and anxiety. Subjects were also characterized with regard to personality traits such as self-efficacy, hostility, and alexithymia. Neuroendocrine activity was assessed by examination of awakening and diurnal salivary cortisol profiles and 24-hour urinary catecholamine excretion. Multiple linear regression analysis was used to analyze posttraumatic stress symptoms at 24-month follow-up as a function of pretraumatic characteristics. RESULTS: A high level of hostility and a low level of self-efficacy at baseline accounted for 42% of the variance in posttraumatic stress symptoms after 2 years. Subjects who had both risk factors at baseline showed a significant increase in measures of PTSD symptoms, depression, anxiety, general psychological morbidity, global symptom severity, and alexithymia during the 2-year period. Biological characteristics were not predictive of the development of psychopathological symptoms. CONCLUSIONS: These results suggest that specific personality traits may constitute markers of vulnerability to the development of psychopathological symptoms after trauma exposure. Early identification of preexisting risk factors is needed to provide effective prevention and intervention for individuals who are at risk of developing trauma-related disorders.

Adult↗

Selective amnesic effects of oxytocin on human memory.

The neuropeptide oxytocin is essential for mammalian parturition and lactation. Recent animal studies suggest that oxytocin is also implicated in the central nervous control of behavior including learning and memory. There has been little investigation, however, of the impact of oxytocin on human memory. The purpose of this study was to investigate the effect of a single dose of intranasal oxytocin on implicit and explicit memory in humans. In a placebo-controlled, double-blind study, 38 healthy men were randomly assigned to receive intranasal oxytocin (24 IU) or placebo 50 min before the study phase (incidental learning). Memory was measured using three different memory tests: an implicit perceptual test (word stem completion), an implicit conceptual test (category-cued semantic association), and an explicit test (cued recall). Due to the reproductive-biological role of oxytocin and the impact of adequate environmental conditions for the stimulation of behavioral effects of oxytocin known from animal research, we used semantic word stimuli with reproduction-related vs. neutral meaning. Oxytocin significantly impaired recall performance as compared with placebo treatment irrespective of the meaning of words in the cued recall test. In the implicit conceptual test, characterized by a deepened information processing, compared with placebo, oxytocin significantly impaired only the overall generation of associated target words with reproduction relevant meaning, whereas no significant difference between oxytocin and placebo was obtained for neutral words. These findings concur with data from animal research suggesting that central oxytocin selectively influences memory performance depending on the kind of memory test used and, more importantly, the psychobiological relevance of stimuli.

Administration, Intranasal↗

Reduced glucocorticoid sensitivity of monocyte interleukin-6 release in male employees with high plasma levels of tumor necrosis factor-alpha.

Cytokine production by monocytes plays a key role in atherosclerosis. In vitro, preincubation of whole blood with tumor necrosis factor (TNF)-alpha regulates interleukin (IL)-6 release from monocytes stimulated with lipopolysaccharide (LPS). We investigated whether plasma levels of TNF-alpha would also relate to LPS-stimulated monocyte IL-6 production and the inhibitory effect of a glucocorticoid on this process. 224 middle-aged men were assigned to three groups according to tertiles of plasma levels of TNF-alpha. Subjects in the highest tertile (high TNF-alpha, n = 75) were compared to those in the lowest (low TNF-alpha, n = 74) and medium tertile (medium TNF-alpha, n = 75), respectively. In vitro monocyte IL-6 release following lipopolysaccharide (LPS)-stimulation was assessed with and without coincubation with incremental doses of dexamethasone. Monocyte glucocorticoid sensitivity was defined as the dexamethasone concentration inhibiting IL-6 release by 50%. Subjects with high TNF-alpha showed more IL-6 release after LPS-stimulation than those with low TNF-alpha (p =.011). Monocyte glucocorticoid sensitivity was lower in subjects with high levels of TNF-alpha than in subjects with low (p =.014) and with medium (p =.044) levels of TNF-alpha. Results held significance when a set of classic cardiovascular risk factors was controlled for. Our findings suggest that elevated plasma levels of TNF-alpha might enhance LPS-stimulated IL-6 release from circulating monocytes. Such a mechanism might contribute to exaggerated monocyte cytokine release in vivo to any LPS-like danger signal such as related to an infection or cellular stress thereby promoting atherosclerosis.

Adult↗