Differential responses of serum and salivary interleukin-6 to acute strenuous exercise

Physical exercise is associated with elevation of serum levels of interleukin-6 (IL-6) because of its production in the muscles. The use of IL-6 measurements in saliva has been proposed in the field of immunopathology, mainly involving salivary gland disease. We evaluated the responses of serum and salivary IL-6 in two different groups of athletes submitted to different types of controlled strenuous exercise (spinning activity and maximal isokinetic test). Serum and salivary samples for IL-6 measurements, and serum samples for lactate and myoglobin determination before and after exercise, were obtained. Salivary IL-6 was measured by ELISA after dilution experiments and compared with results obtained by immunoradiometric assay. Spinning activity elicited significant increases in all the variables, and no correlation was found among the respective variations. A significant response to the isokinetic exercise was observed for serum IL-6, lactate and myoglobin only; no correlation was found between serum and salivary IL-6. Our study demonstrated that serum and salivary IL-6 responses to exercise are dissociated, possibly in relation to the lack of relationships between the systemic/muscular and the salivary routes of IL-6 production. Analytical issues that concern IL-6 measurement in saliva deserve attention, notably regarding the collection method used to absorb saliva. Concomitant monitoring of serum markers of inflammation, muscle metabolism and damage can provide information about muscle function properties and adaptations to physical effort in different types of athletes.     

Sex differences in the interleukin-6 response to acute psychological stress

Interleukin-6 (IL-6), an immune regulator that helps coordinate the inflammatory response, may mediate inflammatory disease exacerbation associated with stress. Twenty men and twenty women completed a single session, comprising baseline (20 min), mental arithmetic task (8 min), and recovery (60 min). Blood samples, taken at baseline, immediately after the task, and at +30 and +60 min recovery were analysed for plasma IL-6. Overall, IL-6 increased linearly from baseline to +60 min recovery, and a sex difference was found in the IL-6 response, with men peaking earlier than women. These findings confirm a small delayed IL-6 increase after acute laboratory stress, and reveal sex differences in the profile of the IL-6 response.     

The psychosocial stress-induced increase in salivary alpha-amylase is independent of saliva flow rate

The stress response of salivary alpha-amylase (sAA) has been suggested as an index for sympathetic nervous system activation. However, concurrent inhibition of the parasympathetic nervous system is discussed as a confounder due to suppression of saliva flow rate. Here we set out to test the influence of stress-induced changes in flow rate on sAA secretion. Twenty-six subjects underwent the Trier Social Stress Test and a control condition. Saliva was sampled by passive drooling or salivettes. Saliva flow rate, sAA levels and output, salivary cortisol, and heart rate variability were measured. Flow rate increased only when sampled by passive drooling. Stress-induced increases in amylase levels were correlated with increases of amylase output but not with flow rate. Results indicate that flow rate is not a confounder of stress-induced sAA activation and suggest that valid measurements of sAA can be obtained by salivettes without the need for assessment of flow rate.     

Salivary dehydroepiandrosterone secretion in response to acute psychosocial stress and its correlations with biological and psychological changes

We investigated dehydroepiandrosterone (DHEA) secretion in response to acute psychosocial stress and the relations of DHEA secretion to cortisol secretion, cardiovascular activity, and negative mood changes. Thirty-three male students (mean age 22.6 years) were subjected to the psychosocial stress test "Trier Social Stress Test" (TSST), in which the participants were asked to deliver a speech and perform a mental arithmetic task in front of two audiences. Collections of saliva, measurements of blood pressure and heart rate, and assessments of negative mood by visual analog scales were conducted before, during, and after TSST. Acute psychosocial stress significantly increased salivary DHEA level by an average of 60% immediately after TSST. The peak of DHEA concentration preceded that of cortisol concentration by about 10 min. DHEA response was moderately correlated to cortisol response (r=.34, r(s)=.49) but not to cardiovascular response. Lower DHEA level and elevated cortisol/DHEA ratio during TSST were significantly and moderately correlated with increased negative mood during and after TSST. These results indicated that an acute increase in DHEA concentration under stressful situations might be partly mediated by the activity of hypothalamus-pituitary-adrenal axis and could have some significance in the improvement of negative mood.     

Effects of panel sex composition on the physiological stress responses to psychosocial stress in healthy young men and women

Men and women differ in regard to psychosocial stress responses. Biological and contextual factors are known to mediate these differences; however, few studies investigated their interaction. In the present study, we examined contributions of both contextual and biological factors to the stress response of young healthy adults. Men and women were exposed to a modified version of Trier Social Stress Test. The participants gave a speech in front of a panel of judges, composed of either male or female panelists. Both men, and women presented a cortisol increase only when exposed to opposite sex panelists. Interestingly, this effect was only observed in women in their follicular phase. This finding showed that the induction of a psychosocial stress response does not strictly rely on direct social evaluation, but also depends on the sex composition of the panel. Implications for future studies are discussed.     

成纤维细胞介导的人白细胞介素6基因疗法的建立及其体内白细胞介素6分泌水平的实验研究

细胞因子基因治疗是近年来生物治疗的重要进展。本文以人IL-6基因为治疗目的基因,以成纤维细胞为载体细胞,建立了人IL-6基因疗法的实验模型,并动态观察了其体内IL-6分泌水平.将650bp的人IL-6 cDNA 插入到携有Neo~R 基因的表达载体BCMGNeo 的Xho I 位点上,对此重组表达载体进行限制性酶切鉴定。用磷酸钙共沉淀法将BCMGNeo-IL-6转入NIH3T3成纤维细胞中,通过G418抗性筛选、有限稀释和上清中IL-6活性的测定,从多株阳性克隆中筛选到一株高分泌IL-6(184.6U/ml)的克隆株。对此阳性克隆进行了Southern 杂交分析。将此阳性克隆体外扩增、包裹入胶原中,然后移植入小鼠腹腔内,可从小鼠血清中(直至移植后15天)检测出IL-6,明成纤维细胞能成功地将IL-6基因导入体内并有效表达,证明该基因疗法是可行的。     

Impact of acute psychosocial stress on peripheral blood gene expression pathways in healthy men

We investigated peripheral blood mononuclear cell gene expression responses to acute psychosocial stress to identify molecular pathways relevant to the stress response. Blood samples were obtained from 10 healthy male subjects before, during and after (at 0, 30, and 60 min) a standardized psychosocial laboratory stressor. Ribonucleic acid (RNA) was extracted and gene expression measured by hybridization to a 20,000-gene microarray. Gene Set Expression Comparisons (GSEC) using defined pathways were used for the analysis. Forty-nine pathways were significantly changed from baseline to immediately after the stressor (p < 0.05), implicating cell cycle, cell signaling, adhesion and immune responses. The comparison between stress and recovery (measured 30 min later) identified 36 pathways, several involving stress-responsive signaling cascades and cellular defense mechanisms. These results have relevance for understanding molecular mechanisms of the physiological stress response, and might be used to further study adverse health outcomes of psychosocial stress.     

Stress-buffering effects of psychosocial resources on physiological and psychological stress response in pregnant women

Sixty healthy pregnant women (aged 21-35 years), including 30 pregnant women at the beginning of second trimester and 30 women at the beginning of third trimester underwent a psychosocial stress test. Physiological (salivary free cortisol levels, salivary alpha-amylase levels) and psychological (perceived stress, mood, anxiety) responses to standardized psychosocial stress have been brought in association with psychosocial resources (self-efficacy and daily uplifts). Predictions revealed that higher resources predict lower physiological and psychological stress responses and higher mood levels. We conclude from our data that psychosocial resources appear to dampen psychological and physiological stress response during pregnancy.     

Allostatic load associations to acute, 3-year and 6-year prospective depressive symptoms in healthy older adults

Allostatic load represents the strain that chronic stress exerts on interconnected biological systems. Associated algorithms are related to numerous deleterious physical outcomes in older populations, and yet few studies have assessed associations to mental health outcomes like geriatric depression. Using data from the Douglas Hospital Longitudinal Study of Normal and Pathological Aging, we assessed whether using an allostatic load index derived from seven biomarkers could detect self-rated depressive symptoms in 58 healthy older adults followed longitudinally over a 6-year period. Our results revealed that increased allostatic load was associated with increased depressive symptoms on the same year of assessment. After 3 years, AL was prospectively associated with depressive symptoms, but entering age and sex as covariates attenuated this effect to a trend. Only age emerged as a significant predictor of depressive symptoms over 6 years. These findings suggest that increased AL in older age is only associated with depressive symptomatology acutely. Over longer periods of time, however, the physical and psychological sequelae of advanced age may contribute to increased depressive symptoms via pathways otherwise undetectable using allostatic load indices of sub-clinical physiological dysregulations.     

Chronic stress, salivary cortisol, and alpha-amylase in children with asthma and healthy children

The present study examined whether chronic stress is related to daily life levels of salivary alpha-amylase (sAA), a marker for sympathetic activity, and cortisol in healthy children versus children with asthma. Children's sAA and cortisol levels were measured repeatedly over 2 days. Chronic stress measures included interviews with children about chronic home life stress and interviews with parents about one marker of socioeconomic status, parental education. Among children with asthma, higher chronic stress was associated with lower daily sAA output, while among healthy children, higher chronic stress was associated with flatter cortisol slopes. In conclusion, chronically stressed children with asthma showed lower salivary alpha-amylase output, indicating lower sympathetic activity, and implying a possible mechanism for increased susceptibility to symptom exacerbations. In contrast, higher cortisol levels in healthy children with chronic stress may indicate, for example, an increased risk for infectious diseases. This dichotomy emphasizes the different biological effects of chronic stress depending on illness status.     

The interleukin-6 promoter polymorphism is associated with elevated leukocyte,lymphocyte, and monocyte counts and reduced physical fitness in young healthy smokers

Smoking and interleukin-6 are important factors in driving inflammation. This study assessed the relationship between smoking, interleukin-6 genotype, physical fitness, and peripheral blood count in healthy young men. For this interleukin-6 promoter polymorphism –174 genotype-phenotype association study 1,929 healthy German male aviators recruited at the central German Air Force Institute of Aviation Medicine were stratified by smoking habits. Cardiovascular fitness was expressed as maximal physical working capacity (PWCmax) in watts per kilogram body weight as assessed by maximal exercise testing by cycle ergometry up to physical exhaustion. Smokers had higher leukocyte and lymphocyte counts than nonsmokers and lower PWCmax. In the overall study population the C allele of the interleukin-6 polymorphism was weakly associated with elevated leukocytes and lymphocytes; in nonsmokers the interleukin-6 polymorphism was not associated with altered phenotypes, but in smokers the interleukin-6 C allele was associated with higher leukocytes, lymphocytes, and monocytes and with lower PWCmax. Smoking is thus associated with elevated leukocytes and lymphocytes and with reduced physical fitness. Gene carriers with the interleukin-6 C allele may suffer particularly from cigarette smoking.Abbreviations CRP C-reactive protein - IL Interleukin - PWCmax Maximal physical working capacity     

Blunted cardiovascular and cortisol reactivity to acute psychological stress: A summary of results from the Dutch Famine Birth Cohort Study

The Dutch Famine Birth Cohort Study is a large population based study of late middle aged, overall healthy men and women whose health has been followed from 50 to 65 years of age. In a sample of 725 cohort members, an extensive psychological stress protocol was performed during which cardiovascular and cortisol responses were measured. In line with many previous studies, results showed that increased blood pressure responsiveness to the stress protocol was associated with an increased risk for hypertension 5 years later. However, decreased cardiovascular and/or cortisol stress reactivity were associated with obesity and the risk of becoming obese, symptoms of depression and anxiety, a poor self-reported health, poor lung function, and poor cognitive function (all p for statistical tests < 0.05). These associations generally survived adjustment for a range of potential confounders, including resting cardiovascular and cortisol activity, commitment to the stress tasks, sex, age, smoking and use of medication. Results from these studies agree with recent evidence that low biological reactivity to acute psychological stress may not always be beneficial for health but instead seems to be a marker for a range of negative health outcomes. Future studies have to point out whether low stress reactivity precedes or follows these negative health outcomes.     

血清IL-6、IL-8在急性心肌梗死缺血-再灌注过程中的动态变化及其临床意义

目的 :探讨血清IL 6、IL 8在急性心肌梗死 (AMI)早期及溶栓治疗过程中的动态变化及其意义。方法 :采用放射免疫分析法对 30例AMI患者入院当时、溶栓前及溶栓后不同时间点的血清IL 6、IL 8进行检测 ,分析其与心肌缺血 再灌注间的关系。结果 :与健康对照组相比 ,所有AMI患者的IL 6、IL 8水平于入院时即已开始升高 ,溶栓治疗后继续升高 ,其中IL 6高峰期在溶栓后 12～ 2 4小时 ,IL 8在 4～ 8小时 ;溶栓再通组升高更明显 (P <0 0 5 ) ;伴有心源性休克 ,急性心力衰竭及严重心律失常并发症的AMI患者较无并发症者增高明显 (P <0 0 5 )。结论 :观察细胞因子IL 6、IL 8动态变化规律有助于判定AMI病情及估价溶栓治疗效果。     

心力衰竭患者T淋巴细胞亚群和IL-6表达的变化

 目的：探讨充血性心力衰竭（CHF）患者T淋巴细胞亚群和白细胞介素-6（IL-6)表达的变化。方法：选择纽约心脏病学会（NYHA）心功能Ⅱ~Ⅳ级的CHF患者48例作为观察组，30例健康查体者作为对照组。用流式细胞仪测定全血T细胞亚群数目，并应用酶联免疫吸附法测定血清和外周血单个核细胞（PBMC）培养上清IL-6含量。结果：CHF 患者CD3、CD4和CD4/CD8显著降低(P<0.05,或P<0.01)，并与CHF程度呈负相关(r=-0.976、-0.826、-0.881;均P<0.01)；CHF患者CD8、血清、PBMC培养上清和IL-2刺激后上清中IL-6均显著高于对照组(均P<0.01)，并与CHF程度呈正相关（r=0.890、0.988、0.984、0.982;均P<0.01）。结论：T细胞亚群数目异常和IL-6表达增加，可能是CHF患者免疫功能异常的机制之一。     

Influence of acute stress on response inhibition in healthy men: An ERP study

The current study investigated the influence of acute stress and the resulting cortisol increase on response inhibition and its underlying cortical processes, using EEG. Before and after an acute stressor or a control condition, 39 healthy men performed a go/no‐go task while ERPs (N2, P3), reaction times, errors, and salivary cortisol were measured. Acute stress impaired neither accuracy nor reaction times, but differentially affected the neural correlates of response inhibition; namely, stress led to enhanced amplitudes of the N2 difference waves (N2d, no‐go minus go), indicating enhanced response inhibition and conflict monitoring. Moreover, participants responding to the stressor with an acute substantial rise in cortisol (high cortisol responders) showed reduced amplitudes of the P3 of the difference waves (P3d, no‐go minus go) after the stressor, indicating an impaired evaluation and finalization of the inhibitory process. Our findings indicate that stress leads to a reallocation of cognitive resources to the neural subprocesses of inhibitory control, strengthening premotor response inhibition and the detection of response conflict, while concurrently diminishing the subsequent finalization process within the stream of processing.     

Salivary cortisol, stress and mood in healthy older adults: the Zenith study

The aims of this study were to investigate the relationship between salivary cortisol, stress and mood and to look at the circadian rhythms of positive (PA) and negative (NA) mood in older adults. The participants were 41 healthy adults aged 55-69 years, recruited in Northern Ireland as part of the European Commission-funded Zenith project. Salivary cortisol samples were obtained twice a day (2.30 p.m. and 10.30 p.m.) for 7 consecutive days in conjunction with momentary measures of positive (PA) and negative mood (NA), using PANAS and a trait measure of perceived stress (Perceived Stress Scale). Salivary cortisol levels were measured using an enzyme-linked immunoassay kit. Higher perceived stress levels were associated with lower afternoon PA (r=-0.46, p=0.003) and higher afternoon (r=0.43, p=0.007) and evening (r=0.45, p=0.004) NA. Lower afternoon PA was correlated with higher evening cortisol concentrations (r=-0.47, p=0.002). Greater afternoon PA variability was associated with higher evening cortisol concentrations (r=0.38, p=0.015). A high intra-class correlation between cortisol and positive mood was found (r=0.67, p=0.009). Previously established rhythms for positive and negative mood were confirmed. Interestingly, there was no association between salivary cortisol levels and perceived stress in these healthy older adults. Further, more extensive research is required to better understand the apparent interplay between these variables and ageing.     

Elevated plasma interleukin-6 levels in trained male triathletes following an acute period of intense interval training

The aim of the present study was to investigate possible changes in the plasma IL-6 levels, subjective reporting of sources and symptoms of stress and the innate immune system in response to an acute period of intensified run training in highly trained endurance athletes. Eight healthy endurance trained male subjects (mean ± SD age 23 ± 2 years, VO_2max 64.8 ± 2.6 ml kg⁻¹ min⁻¹, mass 77.1 ± 2.9 kg) completed the study which took place over a 4 week period. In weeks 2 and 3, in addition to their normal endurance training, subjects completed interval-training run sessions on three successive days. Saliva and venous blood samples were taken at the end of each week. Blood samples were analysed for leukocyte counts; neutrophil function; plasma IL-6; creatine kinase activity; and cortisol. Symptoms and sources of stress were assessed by questionnaire. Plasma IL-6 and creatine kinase activity were elevated following intensified training. Neutrophil function was reduced but total leukocyte and neutrophil counts, plasma cortisol and salivary IgA remained unchanged. There was a worsening in symptoms of stress despite there being no significant change in the sources of stress during intensified training. In conclusion, an acute period of intensified training can induce a suppression of the innate immune system and a chronic elevation in IL-6. This was associated with an increase in fatigue and generalised malaise which lends support to the recent cytokine theories of unexplained, underperformance syndrome.     

pBV—IL—6重组质粒的构建及其在E.coli细胞中的超高表达

本研究通过计算机分析设计、人工合成的寡核苷酸引物进行定点诱变和转译起始区优化,再经 PCR 扩增和体外重组,获得重组质粒 pBV-IL-6,转化大肠杆菌获得重组人白细胞介素6的工程菌 EcoliJM103/pBV-IL-6.结果,表达 IL-6占菌体总蛋白的71%.经 IL-6依赖的小鼠杂交瘤细胞系7TDI 和~(?)H-TdR 掺入法测定表达产物粗提物的 IL-6生物活性为10~6U/L,经凝胶过滤纯化与复性之后 IL-6比活性为10~(?)U/mg.表达产物为缺失 N 端25个氨基酸的人白细胞介素6.     

DHEA and DHEA-S response to acute psychosocial stress in healthy men and women

This study investigates the effect of acute psychosocial stress on serum concentrations of DHEA and DHEA-S in healthy men and women. Twenty men and 19 women (age 30-50 years) underwent Trier Social Stress Test (TSST). Physiological measurements were performed before, directly after the stress test and after 30 mins of recovery. In both men and women, significantly elevated DHEA and DHEA-S levels were observed in response to the stressor. There was a large inter-individual variation in the magnitude of the response, especially for DHEA but no statistical difference between men and women. Magnitude of the change in the levels of DHEA was found to be positively associated with the magnitude of the changes in ACTH, cortisol and heart rate. Furthermore, the results of this study suggest that the capacity to secrete DHEA and DHEA-S during acute psychosocial stress declines with age.