Synergistic effects of psychological and immune stressors on inflammatory cytokine and sickness responses in humans.

Activation of the innate immune system is commonly accompanied by a set of behavioural, psychological and physiological changes known as 'sickness behaviour'. In animals, infection-related sickness symptoms are significantly increased by exposure to psychosocial stress, suggesting that psychological and immune stressors may operate through similar pathways to induce sickness. We used a double-blind, randomised, placebo-controlled design to examine the effect of acute psychological stress on immune and subjective mood responses to typhoid vaccination in 59 men. Volunteers were assigned to one of four experimental conditions in which they were either injected with typhoid vaccine or saline placebo, and then either rested or completed two challenging behavioural tasks. Typhoid vaccine induced a significant rise in participants' serum levels of interleukin-6 (IL-6) and this response was significantly larger in the stress versus rest conditions. Negative mood increased immediately post-tasks, an effect also more pronounced in the vaccine/stress condition. In the vaccine/stress group, participants with larger IL-6 responses had heightened systolic blood pressure responses to tasks and elevated post-stress salivary levels of the noradrenaline metabolite 3-methoxy-phenyl glycol (MHPG) and cortisol. Our findings suggest that, as seen in animals, psychological and immune stressors may act synergistically to promote inflammation and sickness behaviour in humans.

Parental adiposity and cortisol awakening responses in young men and women.

A heightened cortisol awakening response (CAR) is associated with adiposity in middle-aged men, but the causal significance of this effect is not known. We hypothesised that if disturbance in cortisol secretion is involved in the development of overweight and obesity, then it might be present in normal weight adults at increased risk of obesity on account of parental adiposity. The CAR and cortisol profile over the day were measured in 33 men and 62 women aged 18-25 years. Parental adiposity was assessed with figure ratings derived from the Contour Drawing Rating Scale, and these were correlated with parental self-reported body mass index (BMI) in a subset of participants (r=0.66-0.79). In men, a positive association was observed between the CAR and their judgements of their fathers' adiposity after controlling for age, smoking status, time of waking, and the participants' own BMI; the correlation was 0.56 (P=0.008) for the cortisol increase between waking and 30 min, and 0.47 (P=0.028) for the cortisol area under the curve. The correlation between the CAR and fathers' own reported BMI and figures ratings were also significant. The relationship between parental adiposity and the CAR in women was inconsistent, and the associations between the CAR and opposite gender parental adiposity were not significant. Parental adiposity was not related to cortisol output over the rest of the day or to the slope between waking and evening in either sex. The results of this study suggest that disturbances of cortisol secretion may present before the emergence of heightened adiposity in young men at raised risk for obesity.

Changes in financial strain over three years, ambulatory blood pressure, and cortisol responses to awakening.

OBJECTIVE: Chronic psychosocial stress has been associated cross-sectionally with ambulatory blood pressure and with salivary cortisol, but there have been few longitudinal studies of the effects of changes in chronic stress. We assessed the influence of changes in financial strain on ambulatory blood pressure and salivary cortisol. METHODS: Data were analyzed from 160 men and women age 47 to 59 years at the first assessment (T1) who repeated ambulatory monitoring 3 years later (T2). We analyzed change in financial strain as a continuous variable, and specifically compared people who did and did not report an improvement in financial strain. RESULTS: Change in financial strain was associated with change in ambulatory systolic pressure after controlling for T1 ambulatory systolic pressure, gender, socioeconomic position, age, smoking, body mass index, and T1 financial strain (p = .041). Systolic pressure at T2 was lower in the improved financial strain (121.7 +/- 11.2 mm Hg) than in the worse/no change group (125.5 +/- 11.5 mm Hg; p = .029). The corresponding diastolic pressures averaged 78.5 +/- 7.1 mm Hg and 80.7 +/- 7.9 mm Hg, respectively (p = .061). The cortisol awakening response (difference between waking and 30 minutes later) was lower (p = .048) in men who reported improved financial strain, controlling for T1 cortisol response, socioeconomic position, age, smoking, time of waking, and T1 financial strain. There were no differences in the slope of cortisol decline over the day or in evening values. CONCLUSION: These longitudinal data extend cross-sectional findings in showing associations between favorable changes in chronic stress and reduced cardiovascular and neuroendocrine activation in everyday life.

Loneliness and stress-related inflammatory and neuroendocrine responses in older men and women.

Loneliness is a predictor of mortality and increased cardiovascular morbidity. Inflammation is a potential pathway through which loneliness might impact health. The aim of the study was to investigate the relationship between loneliness and inflammatory interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra) and monocyte chemotactic protein-1 (MCP-1) responses to standardized mental stress. A secondary purpose was to evaluate whether individual variations in cortisol responses influenced the hypothesised relationship between loneliness and inflammation. Saliva samples and blood were taken from 524 healthy middle-aged men and women from the Whitehall II cohort at baseline, immediately after the stress tasks and 45min later. Loneliness was measured using the revised UCLA loneliness scale. Greater loneliness was associated with larger IL-6 (p=0.044) and IL-1Ra (p=0.006) responses to psychological stress and higher MCP-1 (p<0.001) levels in women, independently of age, grade of employment, body mass index and smoking status. No associations were observed in men. Cortisol responsivity was inversely related to loneliness in women, with the odds of being a cortisol responder decreasing with increased loneliness independently of covariates (p=0.008). The impact of loneliness on health in women may be mediated in part through dysregulation of inflammatory and neuroendocrine systems.

Adiposity, leptin and stress reactivity in humans.

Evidence suggests that individuals who are more obese may be more responsive to stress. Stress activates the sympathetic nervous system (SNS) and the adipose-tissue cytokine leptin stimulates SNS activity in animals. We examined the relationship between adiposity, leptin and physiological responses to acute laboratory stress in 67 women. We predicted that individuals with greater adiposity and/or higher plasma leptin would be more stress-responsive. Adiposity was unrelated to cardiovascular or neuroendocrine stress reactivity. However, women with larger waists had greater stress-induced increases in plasma leptin and interleukin-1 receptor antagonist (IL-1Ra). Similarly, women with higher basal leptin displayed greater stress-induced increases in heart rate and plasma interleukin-6, and larger decreases in heart rate variability and cardiac pre-ejection period. Heightened cardiovascular and inflammatory stress responses are predictive of future cardiovascular risk. Our findings suggest that the cytokines leptin and IL-1Ra may play a role in the association between obesity, stress and cardiovascular health.

Hostility and physiological responses to laboratory stress in acute coronary syndrome patients.

OBJECTIVE: Evidence suggests that emotional stress can trigger acute coronary syndromes in patients with advanced coronary artery disease (CAD), although the mechanisms involved remain unclear. Hostility is associated with heightened reactivity to stress in healthy individuals, and with an elevated risk of adverse cardiac events in CAD patients. This study set out to test whether hostile individuals with advanced CAD were also more stress responsive. METHODS: Thirty-four men (aged 55.9+/-9.3 years) who had recently survived an acute coronary syndrome took part in laboratory testing. Trait hostility was assessed by the Cook Medley Hostility Scale, and cardiovascular activity, salivary cortisol, and plasma concentrations of interleukin-6 were assessed at baseline, during performance of two mental tasks, and during a 2-h recovery. RESULTS: Participants with higher hostility scores had heightened systolic and diastolic blood pressure (BP) reactivity to tasks (both P<.05), as well as a more sustained increase in systolic BP at 2 h post-task (P=.024), independent of age, BMI, smoking status, medication, and baseline BP. Hostility was also associated with elevated plasma interleukin-6 (IL-6) levels at 75 min (P=.023) and 2 h (P=.016) poststress and was negatively correlated with salivary cortisol at 75 min (P=.034). CONCLUSION: Hostile individuals with advanced cardiovascular disease may be particularly susceptible to stress-induced increases in sympathetic activity and inflammation. These mechanisms may contribute to an elevated risk of emotionally triggered cardiac events in such patients.