Effects on blood pressure and autonomic nervous system function of a 12-week exercise or exercise plus DASH-diet intervention in individuals with elevated blood pressure.

AIM: Hypertension is related to abnormalities in autonomic nervous system (ANS) function, with increased sympathetic output and decreased parasympathetic tone. Lifestyle interventions are the first line of treatment in hypertension, and decreased blood pressure (BP) effects may be related to changes in ANS function. Using heart rate recovery (HRR) from exercise as an index of parasympathetic tone and plasma noradrenaline as an index of sympathetic tone, we investigated the effects of lifestyle interventions on ANS function in patients with elevated BP. METHODS: Sedentary participants with elevated BP were randomly assigned to either an exercise only (N = 25), exercise plus dietary approaches to stop hypertension (DASH) diet (N = 12), or waitlist control (N = 15) 12-week intervention. Plasma noradrenaline was measured at rest and participants performed a peak exercise test before and after the intervention. HRR was calculated as peak heart rate (HR) minus HR at 1 min post-exercise. RESULTS: Heart rate recovery showed a significant group by time interaction; both intervention groups showed increases in HRR from pre- to post-intervention, while waitlist showed no change. Similarly, both exercise plus diet and exercise groups, but not waitlist, showed significant reductions in BP from pre- to post-intervention. Linear regression revealed that BP post-intervention was significantly predicted by change in HRR when controlling for pre-BP, age, gender and BMI. CONCLUSIONS: Lifestyle interventions induced training-reduced BP and altered autonomic tone, indexed by HRR. This study indicates the importance of behavioural modification in hypertension and that increased parasympathetic function is associated with success in reduction of BP.

Trait anger, cynical hostility and inflammation in Latinas: variations by anger type?

Anger and hostility are psychological factors that appear to play a salient role in relation to cardiovascular disease (CVD) risk; however, their association with risk within the Latino population remains relatively unexplored. The current study examined associations between overall trait anger, anger subdimensions (i.e., anger temperament and anger reaction) and cynical hostility with sICAM-1, a marker of cellular adhesion and systemic inflammation related to CVD risk, in a sample of 294 middleaged Mexican-American women. Results showed no association between trait anger or anger temperament and sICAM-1. Anger reaction was marginally associated with sICAM-1 (ß=4.77, p=.06). Cynical hostility was significantly associated with sICAM-1 (ß=5.89, p=.04) even after controlling for demographic, biological and behavioral covariates. The current study provides evidence that specific aspects of anger and hostility relate to physiological pathways that potentially influence CVD risk. Findings are discussed in light of contextual cultural factors.

The attenuating effect of personal mastery on the relations between stress and Alzheimer caregiver health: a five-year longitudinal analysis.

The objectives of this study were to evaluate the impact of personal mastery and caregiving stress on caregiver depressive symptoms and health over time and to examine the moderating effect of mastery on the relations between stress and these outcomes. A total of 130 spousal Alzheimer caregivers completed yearly assessments of personal mastery, role overload, health symptoms and depressive symptoms. Random regression was used to evaluate the relations between time-varying values for stress and mastery in predicting depressive and health symptoms. It was found that variation in depressive symptoms over time was significantly related to role overload (p<0.05) and personal mastery (p<0.001). A significant overload-by-mastery interaction was found for predicting depressive symptoms (p=0.002) and caregiver health (p=0.008), whereby mastery attenuated the effect of stress on these outcomes. We conclude that personal mastery appears to reduce the effects of stress on depression and health outcomes over time.

Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma?

BACKGROUND: Exercise can alter health in children in both beneficial (eg reduced long-term risk of atherosclerosis) and adverse (eg exercise-induced asthma) ways. The mechanisms linking exercise and health are not known, but may rest, partly, on the ability of exercise to increase circulating immune cells. Little is known about the effect of brief exercise, more reflective of naturally occurring patterns of physical activity in children, on immune cell responses. OBJECTIVES: To determine whether (1) a 6-min bout of exercise can increase circulating inflammatory cells in healthy children and (2) the effect of brief exercise is greater in children with a history of asthma. METHODS: Children with mild-moderate persistent asthma and age-matched controls (n = 14 in each group, mean age 13.6 years) performed a 6-min bout of cycle-ergometer exercise. Spirometry was performed at baseline and after exercise. Blood was drawn before and after exercise, leucocytes were quantified and key lymphocyte cell surface markers were assessed by flow cytometry. RESULTS: Exercise decreased spirometry only in children with asthma, but increased (p<0.001) most types of leucocytes (eg lymphocytes (controls, mean (SD) 1210 (208) cells/microl; children with asthma, 1119 (147) cells/microl) and eosinophils (controls, 104 (22) cells/microl; children with asthma, 88 (20) cells/microl)) to the same degree in both groups. Similarly, exercise increased T helper cells (controls, 248 (60) cells/microl; children with asthma, 232 (53) cells/microl) and most other lymphocyte subtypes tested. By contrast, although basophils (16 (5) cells/microl) and CD4+ CD45RO+ RA+ lymphocytes (19 (4) cells/microl) increased in controls, no increase in these cell types was found in children with asthma. CONCLUSIONS: Exercise increased many circulating inflammatory cells in both children with asthma and controls. Circulating inflammatory cells did increase in children with asthma, but not to a greater degree than in controls. In fact, basophils and T helper lymphocyte memory transition cells did not increase in children with asthma, whereas they did increase in controls. Even brief exercise in children and adolescents robustly mobilizes circulating immune cells.

Body fat and circulating leukocytes in children.

OBJECTIVE: To determine the effects of obesity on baseline levels of circulating granulocytes, monocytes, and lymphocyte subtypes in otherwise healthy children. DESIGN: Two group comparison of leukocytes in normal weight control and overweight children. SUBJECTS: In total, 38 boys and girls, ages 6-18 years, divided in two groups: normal weight, (NW, BMI<85th %tile, n=15) and overweight (OW, body mass index (BMI)>85th %tile, n=23). MEASUREMENTS: BMI obtained from direct measures of height and body mass. Body fat was assessed by DEXA. Complete blood counts (CBC) were obtained by standard clinical hematology methods and surface antigen staining by flow cytometry. RESULTS: The OW group compared to the NW group had increased total leukocytes counts (P=0.011), neutrophils (P=0.006), monocytes (P=0.008), total T (CD3) lymphocytes (P=0.022), and Helper T (CD4(+)) cells (P=0.003). Significant correlations were evident between leukocytes, and BMI percentile, BMI, or percent body fat. Neither lean body mass nor VO(2peak) per unit lean body mass were significantly related to any of the leukocytes. Percent body fat and BMI percentile were positively correlated (P<0.05) to total T cells (CD3) and/or helper T cells (CD4(+)). CONCLUSION: A group of 23 overweight children displayed elevated counts in most types of circulating immune cells, suggesting the presence of low-grade systemic inflammation, a known pathogenetic mechanism underlying most long-term complications of obesity. Our data provide an additional rationale for the importance of avoiding or correcting pediatric obesity.

Effect of intense wrestling exercise on leucocytes and adhesion molecules in adolescent boys.

BACKGROUND: In adults, exercise is a powerful and natural stimulator of immune cells and adhesion molecules. Far less is known about exercise responses during childhood and adolescence and whether or not exercise in "real life" activities of healthy adolescents influences immune responses. OBJECTIVE: To determine if strenuous exercise leads to significant changes in leucocyte number and adhesion molecule expression in adolescent boys. METHODS: Eleven healthy, high school boys, aged 14-18.5 years, performed a single, typical, 1.5 hour wrestling practice session. Blood was sampled before and after the session. Flow cytometry was used to evaluate changes in immune responses. RESULTS: The exercise led to significant (p<0.05) and robust increases in granulocytes, monocytes, and all lymphocyte subpopulations. The most significant changes were observed for natural killer cells (p<0.0005). The number of T cytotoxic and T helper cells expressing CD62L increased significantly (p<0.002 and p<0.0005 respectively), as did the number of T cytotoxic and T helper cells not expressing CD62L (p<0.003 and p<0.009 respectively). The density of CD62L on lymphocytes decreased significantly with exercise (p<0.0005), whereas CD11a (p<0.01) and CD54 (p<0.01) increased. CONCLUSIONS: The data show that an intense wrestling bout in adolescent boys leads to profound stimulation of the immune system. The role of these common changes in overall immune status and the development of the immune and haemopoietic systems has yet to be determined.

A randomised-controlled trial of the effects of a traditional herbal supplement on sleep onset insomnia.

OBJECTIVES: To study the effectiveness and safety of a traditional herbal supplement used for sleep onset insomnia. DESIGN: A double-blind, randomized, placebo-controlled, cross-over study. SETTING: A total of 25 healthy volunteers (20-65 years of age) suffering from sleep onset insomnia were recruited from the general population. INTERVENTION: A traditional Ayurvedic supplement formulated to reduce sleep onset insomnia. MAIN OUTCOME MEASURE: Sleep latency. RESULTS: The supplement led to a statistically significant decrease in reported sleep latency of 16.72 min (S.D.=44.8) as compared to placebo (P=0.003). There were no self-reported side effects. CONCLUSIONS: The findings suggest that traditional herbal supplements may be of significant benefit to patients suffering from sleep onset insomnia while avoiding the negative side effects of commonly prescribed hypnotics.

Peripheral leukocyte subpopulations and catecholamine levels in astronauts as a function of mission duration.

OBJECTIVE: The objective of this study was to determine the effects of spaceflight duration on immune cells and their relationship to catecholamine levels. METHODS: Eleven astronauts who flew aboard five different US Space Shuttle flights ranging in duration from 4 to 16 days were studied before launch and after landing. RESULTS: Consistent with prior studies, spaceflight was associated with a significant increase in the number of circulating white blood cells (p <.01), including neutrophils (p <.01), monocytes (p <.05), CD3+CD4+ T-helper cells (p <.05), and CD19+ B cells (p <.01). In contrast, the number of CD3-CD16+56+ natural killer cells was decreased (p <.01). Plasma norepinephrine levels were increased at landing (p <.01) and were significantly correlated with the number of white blood cells (p <.01), neutrophils (p <.01), monocytes (p <.01), and B cells (p <.01). Astronauts who were in space for approximately 1 week showed a significantly larger increase on landing in plasma norepinephrine (p =.02) and epinephrine (p =.03) levels, as well as number of circulating CD3+CD4+ T-helper cells (p <.05) and CD3+CD8+ T-cytotoxic cells (p <.05) as compared with astronauts in space for approximately 2 weeks. CONCLUSIONS: The data suggest that the stress of spaceflight and landing may lead to a sympathetic nervous system-mediated redistribution of circulating leukocytes, an effect potentially attenuated after longer missions.

Effect of continuous positive airway pressure and placebo treatment on sympathetic nervous activity in patients with obstructive sleep apnea.

STUDY OBJECTIVES: We studied the effect of continuous positive airway pressure (CPAP) treatment on sympathetic nervous activity in 38 patients with obstructive sleep apnea. DESIGN: Randomized, placebo-controlled trial. SETTING: Patients underwent polysomnography on three occasions in a clinical research center, and had BP monitored over 24 h at home. All of the patients had sleep apnea with a respiratory disturbance index (RDI) > 15. INTERVENTIONS: The patients were randomized blindly to CPAP or placebo (CPAP at ineffective pressure) treatment. MEASUREMENTS AND RESULTS: Prior to therapy, the number of apneas and the severity of nocturnal hypoxia correlated significantly with daytime urinary norepinephrine (NE) levels, but not nighttime urinary NE levels. CPAP treatment lowered daytime BP from 99 +/- 2 mm Hg to 95 +/- 3 mm Hg (mean +/- SEM) and nighttime BP from 93 +/- 3 mm Hg to 88 +/- 3 mm Hg. Placebo CPAP treatment decreased both day and night mean BP only 2 mm Hg. CPAP, but not placebo, treatment lowered daytime plasma NE levels by 23%, daytime urine NE levels by 36%, daytime heart rate by 2.6 beats/min, and increased lymphocyte beta(2)-adrenergic receptor sensitivity (all p < 0.05). The effect of CPAP treatment on nighttime urine NE levels and heart rate did not differ from placebo treatment. There was a suggestion of an effect of placebo CPAP treatment on nighttime measures, but not on daytime measures. CONCLUSION: We conclude that daytime sympathetic nervous activation is greater with more severe sleep apnea. CPAP treatment diminished the daytime sympathetic activation; the potential nighttime effect of CPAP treatment was obscured by a small placebo effect.

Effects of psychological stress and psychiatric disorders on blood coagulation and fibrinolysis: a biobehavioral pathway to coronary artery disease?

OBJECTIVE: A hypercoagulable state before overt thrombosis resulting from an imbalance between the coagulation and fibrinolysis systems is related to cardiovascular disease progression and acute coronary syndromes. Psychological stressors and depressive and anxiety disorders also are associated with coronary artery disease. This review explores whether changes in blood coagulation, anticoagulant, and fibrinolytic activity may constitute psychobiological pathways that link psychological factors with coronary syndromes. METHODS: Literature on coagulation, anticoagulation, and fibrinolysis measures in conjunction with psychological factors (mental stress, psychosocial strain, and psychiatric disorders) was identified by MEDLINE search back to 1966 and through checking the bibliographies of these sources. Sixty-eight articles were critically reviewed. RESULTS: In healthy subjects, acute mental stress simultaneously activates coagulation (ie, fibrinogen or von Willebrand factor) and fibrinolysis (ie, tissue-type plasminogen activator) within a physiological range. In patients with atherosclerosis and impaired endothelial anticoagulant function, however, procoagulant responses to acute stressors may outweigh anticoagulant mechanisms and thereby promote a hypercoagulable state. Chronic psychosocial stressors (job strain or low socioeconomic status) are related to a hypercoagulable state reflected by increased procoagulant molecules (ie, fibrinogen or coagulation factor VII) and by reduced fibrinolytic capacity. There is also some evidence that points to hypercoagulability in depression. CONCLUSIONS: Different categories of psychological measures to varying extent are associated with characteristic patterns of coagulation and fibrinolysis activity. Associations between psychological factors and several coagulation and fibrinolysis variables related to atherosclerosis provide a plausible biobehavioral link to coronary artery disease.

The hypercoagulable state in sleep apnea is related to comorbid hypertension.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with increased prevalence of atherosclerotic disease. A hypercoagulable state thought to underly atherosclerosis has been described in both OSA and systemic hypertension. We wondered about the respective contribution of apnea and hypertension to a hypercoagulable state. DESIGN: Eighty-seven subjects with symptoms suggestive of OSA, mean age 47 years (range 32-64 years), underwent polysomnography and blood pressure (BP) screening. OSA was diagnosed when respiratory disturbance index (RDI) > or = 15. Subjects having systolic BP (SBP) > 140 mmHg and/or diastolic BP (DBP) > 90 mmHg were classified as having hypertension. Three hypercoagulability markers were measured: thrombin/antithrombin III complex (TAT), fibrin D-dimer (DD), and von Willebrand factor antigen (vWF:ag). RESULTS: Analysis of variance and multiple linear regression were performed on the following four subject groups: (1) normotensive non-apneics (n = 19), (2) normotensive apneics (n = 38), (3) hypertensive non-apneics (n = 11), and (4) hypertensive apneics (n = 19). OSA (groups 2 and 4) had no significant main effect on hemostasis. Hypertensives (groups 3 and 4) had higher plasma levels of TAT (median/inter-quartile range, 148/59-188 versus 77/53-108 pmol/l; P = 0.009) and of DD (376/265-721 versus 303/190-490 ng/ml; P = 0.040) than normotensives (groups 1 and 2). Across all subjects, SBP was the only significant predictor of TAT (P = 0.001) and of DD (P = 0.004), whereas DBP was the only significant predictor of vWF:ag (P = 0.029). These findings persisted even after controlling for gender, age, body mass index, RDI, mean SaO2, and hematocrit. CONCLUSION: Hypercoagulability in OSA is mediated by comorbid hypertension and might account for high cardiovascular morbidity in OSA in general.

Short-term hyperglycemia induces lymphopenia and lymphocyte subset redistribution.

Alterations in lymphocytes are a common finding in both type I and type II diabetes. Autoimmune phenomena in type I diabetes, the stage of the diabetic disorder and metabolic effects of therapeutic interventions may also affect actual distribution of lymphocyte phenotypes. This study investigated immunological effects specific to standardized hyperglycemia in non-diabetic individuals to exclude immunological changes potentially related to diabetes stage and treatment. 37 subjects (mean age +/- SD 39 +/- 5 years) underwent a sequence-controlled crossover with oral administration of a solution containing either 75 g glucose or artificial sweetener (i.e. placebo). At rest and at two hours, counts of white blood cells (WBC), mixed lymphocytes, mature T-cells (CD3), T-helper cells (CD4), T-suppressor/ cytotoxic cells (CD8), B-cells (CD19), natural killer cells (CD16/CD56), and interleukin-2 receptor bearing peripheral blood mononuclear cells (CD25) were measured by flow cytometry. Subjects showed a significant decrease in WBC, lymphocytes, and all lymphocyte subsets with the OGTT compared with the placebo solution (p < .05 to p < .001). In non-diabetic individuals, short-term hyperglycemia induces immunological changes that may be relevant to explain similar findings in patients with diabetes mellitus. Future studies need to validate these findings and their potential clinical implications in a diabetic population.

Catecholamines in human saliva.

Catecholamines are readily detectable in human saliva but their origin is unclear. Norepinephrine (NE) was stable in saliva stored at 4 degrees for 2 hours but 11 +/- 3% degraded after storage at 25 degrees for 1 hour. We intravenously infused 3H-NE into humans and measured levels of 3H-NE and its metabolites in both saliva and forearm venous plasma (a site whose plasma NE levels reflect both local uptake and release of NE). 3H-NE levels in saliva continued to rise for 1 hour even though forearm plasma levels had plateaued by 5 min. By 65 min into the infusion the ratio of 3H-NE:non-radioactive NE was similar in saliva and forearm venous plasma. The ratio of NE:epinephrine (E) was similar in saliva and forearm venous plasma at all time points. Chewing induced salivation, and at least tripled the amount of NE, E and 3H-NE released into saliva per minute, but decreased their concentration in saliva by as much as one half. Saliva NE level was unaltered after 15 min of standing but was increased by 31% after 1 hour of upright posture. Our data imply that the NE present in human saliva comes from both the bloodstream and from salivary sympathetic nerves. The finding that diffusion of blood NE into saliva takes roughly 1 hour to complete suggests that NE in saliva is a poor index of acute changes in sympathetic activity.

Continuous positive airway pressure normalizes cardiac autonomic and hemodynamic responses to a laboratory stressor in apneic patients.

OBJECTIVES: We examined the effect of continuous positive airway pressure (CPAP) treatment for sleep apnea on cardiac contractility, heart rate variability, and hemodynamics at rest and in response to a laboratory stressor. SUBJECTS AND INSTRUMENTATION: Forty-one apneic patients were studied on three occasions: before treatment, after 1 full night of CPAP treatment, and after 1 week of CPAP treatment. The subjects were randomly assigned to receive effective treatment or placebo. Contractility and hemodynamics were determined with impedance cardiography, and parasympathetic activity was assessed by analysis of heart rate variability. Measures were determined at rest and in response to a stressor. DESIGN AND RESULTS: For the cardiac sympathetic (contractility) measures (preejection period, cardiac acceleration index [CAI], and low-frequency/high-frequency ratio) significant interactions were found in the combination treatment (CPAP vs placebo) by study day (day 1, day 3, day 11) by test period (baseline, preparation, talking) [p < 0.01]. For these measures, there were no differences between the treatment groups or responses to the stressor on day 1. Levels in placebo-treated subjects did not change or respond on the subsequent study days. In the CPAP-treated subjects, there was a decrease in these indexes at baseline, which became significantly lower by day 11 (ie, CAI levels were 24 Omega/s(2), 22 Omega/s(2), and 14 Omega/s(2) on day 1, day 3, and day 11, respectively). These measures also became responsive to the stressor by showing increased sympathetic activity (CAI levels on day 11 were 14 Omega/s(2) at baseline, 32 Omega/s(2) during speech preparation, and 36 Omega/s(2) while speaking). The parasympathetic indexes, such as high-frequency power or band of heart rate variability as determined by spectral analysis, showed a significant day-by-treatment interaction (p < 0.005), whereas the CPAP- treated group had significantly more parasympathetic activity after 1 week of treatment. For the hemodynamic measures (stroke volume [SV], cardiac output, and systemic vascular resistance [SVR]), there were significant treatment-by-study day-by-test-period interactions (p < 0.01). SV and cardiac output increased across days, and SVR decreased in the CPAP-treated patients. CONCLUSIONS: These results indicate that CPAP normalizes contractility, increases cardiac vagal tone, and changes hemodynamic regulation from being resistance dominated to being cardiac dominated. Thus, after 1 week of treatment with CPAP, many of the indicators of poor cardiac functioning in apnea patients are improved.

Effects of laboratory versus field exercise on leukocyte subsets and cell adhesion molecule expression in children.

In adults, exercise is a powerful and natural stimulator of immune cells and adhesion molecules. Far less is known about these exercise responses during childhood and whether or not exercise in real-life activities of healthy children might influence immune responses. We compared laboratory exercise (10 x 2 min periods of heavy, constant intensity, cycle ergcometer exercise with 1 min rests between exercise in nine subjects, aged 9-15 years) with field exercise (90 min soccer practice in nine different subjects, aged 9-11 years). Blood was sampled before both protocols, 5 min after the 30 min laboratory protocol, and 10-15 min after the 90 min field protocol. Both field and laboratory exercise protocols led to significant (P<0.05) increases in granulocytes, monocytes, and all lymphocyte subpopulations. The mean (SEM) increases were similar for the two protocols except for the significantly greater increase in laboratory compared with field protocols for natural killer cells [142 (39)% vs 12 (16)%, P<0.001] and monocytes [64 (22)% vs 32 (19)%, P<0.001] Both protocols significantly influenced adhesion molecules (such as CD54) which have not been previously studied in children. However, the adhesion molecule CD8+ CD62L increased to a significantly (P < 0.001) greater extent in the laboratory [101 (25)%] versus field [34 (25)%] protocol. Finally, the density of CD632L on lymphocytes significantly decreased with laboratory exercise but showed no change in the field protocol [-20 (3)% vs -3 (3)%, P<0.001]. The rapid and substantial immune response in both laboratory and field protocols suggests that exercise stimulation of the immune system occurs commonly in the real lives of children and may play a role in their overall immune status.

Propranolol affects stress-induced leukocytosis and cellular adhesion molecule expression.

In this study, the impact of the beta-adrenergic antagonist propranolol on resting and acute psychological- and physical-stress-induced circulating leukocyte numbers and the density of cellular adhesion molecules was investigated. In a randomized double-blind crossover design, 45 healthy volunteers performed a 15-min public speaking task and 21 subjects performed a 16-min bicycle exercise after 5 days of ingesting a placebo and after 5 days of ingesting 100 mg/day propranolol. One week of ingesting propranolol modestly elevated the numbers of CD62L+ (P<0.019) but not CD62L- T-lymphocytes. Moreover, propranolol preferentially blunted-psychological stress-induced increases in naïve T-helper (CD4+CD62L+; P<0.049) and naïve T-cytotoxic lymphocytes (CD8+CD62L+; P<0.003), as well as activated T-cytotoxic lymphocytes (CD8+CD29+; P<0.005). However, exercise-induced increases in leukocyte numbers were enhanced following propranolol treatment (P<0.04). In contrast to the effect on the numbers of adhesion-molecule-bearing cells, there was only a modest effect of propranolol on stress-induced alterations of the density of CD62L, CD54 and CD11a. In this study, propranolol treatment interfered with the adrenergic regulation of circulating leukocyte numbers by blunting psychological stress effects but enhancing exercise effects. Propranolol affected the cell activation status to a lesser extent, as reflected by the density of adhesion molecules.

Acute psychological stress and exercise and changes in peripheral leukocyte adhesion molecule expression and density.

OBJECTIVE: This study examined the effects of acute psychological stress and exhaustive exercise on the expression and density of adhesion molecules (L-selectin, lymphocyte function antigen-1 [LFA-1], and intracellular adhesion molecule-1 [ICAM-1]) on monocytes, granulocytes, and lymphocytes. METHODS: Forty-five healthy volunteers performed a 15-minute public speaking task and a 15- to 18-minute bicycle ergometer challenge. RESULTS: In general, both the exercise and speaking tasks led to increases in the number of circulating leukocytes and lymphocyte subsets. The density of L-selectin (CD62L) on mixed lymphocytes and T lymphocytes was decreased in response to exercise (p values < .001). Both stressors led to an increased density of LFA-1 (CD11a) on mixed lymphocytes (p values < .01), whereas CD11a density on monocytes and granulocytes remained unchanged. ICAM-1 (CD54) density was unaffected, but the number of lymphocytes, monocytes, and granulocytes expressing CD54 increased in the circulation on both stressors. CONCLUSIONS: The data indicate that both psychological stress and exercise have significant effects on cellular expression of adhesion molecules on circulating leukocytes. Given the crucial role that adhesion molecules on circulating cells play in inflammation and disease, these findings may have clinical relevance in sympathetic nervous system-induced immune activation.

Interleukin-6 and tumor necrosis factor-alpha production after acute psychological stress, exercise, and infused isoproterenol: differential effects and pathways.

OBJECTIVE: The aim of the study was to assess the effects of three different methods of acute activation of the sympathetic nervous system on lipopolysaccharide-induced in vitro production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). METHODS: Thirty-two healthy volunteers performed speech and exercise tasks and underwent a 30-minute infusion of isoproterenol. RESULTS: As expected, acute activation of the sympathetic nervous system led to leukocytosis, including increases in lymphocyte, monocyte, and granulocyte populations (p values <.05). Lipopolysaccharide-induced IL-6 production was increased after both the speaking and exercise tasks (p values <.001), whereas TNF-alpha production was elevated only after exercise (p<.05). In contrast, infusion of isoproterenol inhibited TNF-alpha production (p<.001) and caused no change in IL-6 production. CONCLUSIONS: In response to the challenges, IL-6 and TNF-alpha production showed different profiles. Purely beta-agonist stimulation led to downregulation of TNF-alpha production, providing evidence of the antiinflammatory effect of in vivo beta-receptor activation. The enhanced production of both cytokines after exercise, and of IL-6 after the speech task, can be best explained by a simultaneous upregulation of proinflammatory and inflammation-responding mediators. These effects may have an important role in controlling the immune response to acute psychological and physical stress.