Affective and inflammatory responses among orchestra musicians in performance situation

A number of studies have shown that mental challenge under controlled experimental conditions is associated with elevations in inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). However, relatively little work has been done on the effects of ‘naturalistic’ stressors on acute changes in inflammatory markers. The present study examined whether perceived arousal, valence and dominance in musicians are associated with pro-inflammatory and oxidative responses to a concert situation. Blood and salivary samples obtained from 48 members of a symphony orchestra on the day of rehearsal (i.e. control situation) and on the following day of premiere concert (i.e. test situation) were used to determine changes in salivary cortisol, pro-inflammatory markers (plasma myeloperoxidase, serum CRP, plasma IL-6), oxidative stress markers (paraoxonase1 activity and malondialdehyde), and homocysteine, a risk factor for vascular disease. Results of regression analyses showed a significant trend to increased myeloperoxidase (MPO) response in individuals with low valence score. Both affective states, valence and arousal, were identified as significant predictors of cortisol response during concert. In addition, control levels of plasma malondialdehyde were positively correlated with differences in IL-6 levels between premiere and rehearsal (r = .38, p = .012), pointing to higher oxidative stress in individuals with pronounced IL-6 response. Our results indicate that stress of public performance leads to increased concentrations of plasma MPO (20%), IL-6 (27%) and salivary cortisol (44%) in musicians. The decreasing effect of pleasantness on the MPO response was highly pronounced in non-smokers (r = −.60, p < .001), suggesting a significant role of emotional valence in stress-induced secretion of MPO. Additional studies are needed to assess the generalizability of these findings to other ’naturalistic’ stress situations.     

The diurnal patterns of salivary interleukin-6 and C-reactive protein in healthy young adults

In recent years, salivary inflammatory markers, such as interleukin-6 (IL-6) and C-reactive protein (CRP), have been investigated regarding their relationships with psychosocial stress and stress-related diseases. This study investigated the diurnal patterns of salivary IL-6 and CRP in healthy young adults. Twenty-seven students (11 males and 16 females) participated in this study. The participants were instructed to provide saliva samples 8 times a day (at 0700, 0730, 1000, 1300, 1600, 1900, 2200, and 0100 h). For the duration of study, they were asked to wake up at 0700 h and go to bed after 0100 h. Twelve of the participants were asked to repeat this sampling procedure on two consecutive days to test the stability of the diurnal patterns. The salivary IL-6 levels peaked at awakening, gradually declined from morning to noon, and peaked again at midnight, before the participants went to sleep. The salivary CRP levels peaked at awakening, and they were lower during the daytime. The salivary IL-6 and CRP levels exhibited moderate to high stability over 2 days of sample collection. This study revealed that the salivary inflammatory markers had distinctive diurnal patterns.     

Association between brain natriuretic peptide,markers of inflammation and the objective and subjective response to cardiac resynchronization therapy

Introduction: Studies suggest that cardiac resynchronization therapy (CRT) can induce a decrease in brain natriuretic peptide (BNP) and systemic inflammation, which may be associated with CRT-response. However, the evidence is inconclusive. We examined levels of BNP and inflammatory markers from pre-CRT implantation to 14 months follow-up in CRT-responders and nonresponders, defined by two response criteria. Methods: We studied 105 heart failure patients implanted with a CRT-defibrillator (68% men; age = 65.4 ± 10.1 years). The objective CRT-response was defined as a reduction of ⩾15% in left ventricular end systolic volume; subjective CRT-response was defined as an improvement of ⩾10 points in patient-reported health status assessed with the Kansas City Cardiomyopathy Questionnaire. Plasma BNP and markers of inflammation (CRP, IL-6, TNFα, sTNFr1 and sTNFr2) were measured at three time points. Results: Pre-implantation concentrations of TNFα were significantly lower for subjective responders compared to nonresponders (p = .05), but there was no difference in BNP and the other inflammatory markers at baseline. Objective CRT-response was significantly associated with lower BNP levels over time (F = 27.31, p < .001), and subjective CRT-response with lower TNFα levels (F = 5.67, p = .019). Conclusion: Objective and subjective response to CRT was associated with lower levels of BNP and TNFα, respectively, but not with other markers of inflammation. This indicates that response to CRT is not automatically related to a stronger overall decrease in inflammation. Large-scale studies are warranted that further examine the relation between the clinical effects of CRT on inflammatory markers, as the latter have been associated with poor prognosis in heart failure.     

Gender differences in the association of sleep apnea and inflammation

Over the last 15 years, many studies have established an association of sleep apnea with inflammation and metabolic aberrations. However, no controlled studies have examined potential gender effects in this association. We recruited 120 middle-aged, predominantly non-obese mild-to-moderate sleep apneics and controls (62 males, 58 females). All participants underwent a clinical history, physical examination, and 1-night 8-h polysomnography recording and provided a single fasting blood sample for assessment of interleukin-6 (IL-6), tumor necrosis factor receptor 1 (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels. Among non-sleep apneics, females had higher levels of TNFR1 (p = 0.01), CRP (p = 0.005), leptin (p < 0.001), and adiponectin (p < 0.001) compared to males, independent of age and body mass index. When analyzed separately by gender, sleep apneic men had elevated TNFR1 (p = 0.04), CRP (p = 0.06) and IL-6 (p = 0.11) relative to control men; in sleep apneic females, only CRP was elevated (p = 0.04). Furthermore, CRP was associated with apnea severity in a dose–response manner (p-linear = 0.04 in both genders) and was independently associated with comorbid hypertension in apnea (p-linear = 0.005 for women; p-linear = 0.09 for men). In conclusion, although women have naturally higher levels of inflammatory and metabolic markers than men, sleep apneic men appear to have a more severe inflammatory profile compared to women. Our findings suggest that these markers should be analyzed and interpreted separately in men and women, and that a single measure of plasma CRP appears to be a clinically-useful marker of apnea severity and comorbid cardiovascular morbidity.     

Self-reported experiences of everyday discrimination are associated with elevated C-reactive protein levels in older African-American adults

Self-reported experiences of “everyday” discrimination have been linked to indices of cardiovascular disease and overall mortality and findings have been particularly pronounced for African-American populations. However, the biological mechanisms underlying these associations remain unclear. C-reactive protein (CRP), a marker of inflammation, is a known correlate of cardiovascular and other health outcomes and has also been linked to several psychosocial processes. To our knowledge, no studies have examined the association between experiences of discrimination and CRP. We examined the cross-sectional association between self-reported experiences of discrimination and CRP in a sample of 296 older African-American adults (70% female, mean age = 73.1). Experiences of discrimination were assessed with the 9-item everyday discrimination scale and CRP was assayed from blood samples. In linear regression models adjusted for age, sex and education, experiences of discrimination were associated with higher levels of CRP (B = .10, p = .03). This association remained significant after additional adjustments for depressive symptoms (B = .10, p = .04), smoking, and chronic health conditions (heart disease, diabetes, hypertension) that might influence inflammation (B = .11, p = .02). However, results were attenuated when body mass index (BMI) was added to the model (B = .09, p = .07). In conclusion, self-reported experiences of everyday discrimination are associated with higher levels of CRP in older African-American adults, although this association is not completely independent of BMI.     

Cerebrospinal fluid inflammatory markers in Parkinson’s disease – Associations with depression,fatigue, and cognitive impairment

Neuroinflammation may be involved in the pathophysiology of Parkinson’s disease (PD) and specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. The aim of this study was to measure inflammatory markers in cerebrospinal fluid (CSF) samples from PD patients and a reference group, and to investigate correlations between non-motor symptoms and inflammation.We quantified C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein 1-β in CSF samples from PD patients (N = 87) and the reference group (N = 33). Sixteen of the PD patients had a dementia diagnosis (PDD). We assessed symptoms of fatigue, depression, anxiety and cognitive function using the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and the Mini Mental State Examination, respectively.There were no significant differences in mean levels of inflammatory markers between PD patients and the reference group. After controlling for age, gender and somatic illness, patients with PDD had significantly higher levels of CRP compared to non-demented PD patients (p = 0.032) and the reference group (p = 0.026). Increased levels of inflammatory markers in CSF were significantly associated with more severe symptoms of depression, anxiety, fatigue, and cognition in the entire PD group. After controlling for PD duration, age, gender, somatic illness and dementia diagnosis, high CRP levels were significantly associated with more severe symptoms of depression (p = 0.010) and fatigue (p = 0.008), and high MCP-1 levels were significantly associated with more severe symptoms of depression (p = 0.032).Our results indicate that non-motor features of PD such as depression, fatigue, and cognitive impairment are associated with higher CSF levels of inflammatory markers.     

Disturbed sleep is associated with increased C-reactive protein in young women

Evidence links disturbed sleep with an exaggerated inflammatory response and increased risk of adverse health outcomes. An emerging risk factor for many adverse health outcomes is chronic, low-grade inflammation. An exaggerated inflammatory response could provide a biological link between disturbed sleep and adverse health outcomes. The relationship between sleep and chronic, low-grade inflammation has been sparsely examined in otherwise healthy, young women. We evaluated cross-sectional relationships between self-reported sleep and three inflammatory markers. Participants were community dwelling nonpregnant women (N = 43, 28.2 ± 5.2 years of age). Measures included the Pittsburgh Sleep Quality Index (PSQI), sleep diaries, and serum levels of IL-6, TNF-α and C-reactive protein. Poor sleep quality and continuity were associated with higher CRP levels after controlling for covariates. No significant relationships were observed between PSQI scores and IL-6 or TNF-α; sleep duration was not related to any of the inflammatory markers. Poor sleep, in young adulthood, may contribute to the chronic, low-grade inflammation associated with an increased risk for future adverse health outcomes. Future work should longitudinally evaluate how these relationships may affect development of gender-specific diseases in apparently healthy young women.     

Sex differences in the association between stressor-evoked interleukin-6 reactivity and C-reactive protein

Individuals differ consistently in the magnitude of their inflammatory responses to acute stressors, with females often showing larger responses than males. While the clinical significance of these individual differences remains unclear, it may be that greater inflammatory responses relate to increased systemic inflammation and thereby risk for chronic inflammatory disease. Here, we examined whether acute stressor-evoked interleukin (IL)-6 responses associate with resting levels of C-reactive protein (CRP), a marker of systemic inflammation, and whether this association differs by sex. Subjects were 57 healthy midlife adults (30–51 years; 33% female; 68% white). Blood was drawn before and 30-min after two mental stress tasks: a multisource interference task and a Stroop color word task. Hierarchical regressions controlling for age, sex, race, and BMI tested whether stressor-evoked IL-6 responses were associated with resting CRP and whether this association differed by sex. Results indicated that sex and stressor-evoked IL-6 responses interacted to predict CRP (ΔR² = 0.08, B = −1.33, β = −0.39, p = 0.02). In males, larger stressor-evoked IL-6 responses associated with higher CRP, whereas in females, stressor-evoked IL-6 responses showed a non-significant negative association with CRP. These findings indicate that inflammatory responses to acute stressors associate with resting levels of CRP; however, this association differs by sex. Previous literature suggests that there are sex differences in stressor-evoked IL-6 responses, but this is the first study to show sex differences in the relationship between acute inflammatory responses and systemic inflammation. The contribution of these sex differences to inflammatory disease risk warrants further investigation.     

A population-based study of atopic disorders and inflammatory markers in childhood before psychotic experiences in adolescence

ObjectiveSchizophrenia is associated with atopy and increased inflammatory markers. We report a population-based longitudinal study of the associations between childhood atopic disorders, subsequent serum inflammatory markers, interleukin 6 (IL-6) and C-reactive protein (CRP), and the risk of psychotic experiences (PEs).MethodPEs were assessed at age 13 years (n = 6785). Presence of clinician-diagnosed atopic disorders (asthma and eczema) was determined from parent-completed questionnaires at age 10 years (n = 7814). Serum IL-6 and CRP were measured at age 9 years (n = 5076). Logistic regression examined the association between (1) atopy and PEs, (2) inflammatory markers and PEs, and (3) mediating effects of inflammatory markers on the atopy–PEs association. Linear regression examined the association between atopy and inflammatory markers. Age, gender, social class, ethnicity and body mass index were included as potential confounders.ResultsAt age 10 years, about 14% of the sample was reported to have asthma, 12% eczema, and 7% both asthma and eczema. Compared with children with no atopy, risk of PEs at age 13 years was increased for all of these groups; adjusted odds ratios (95% CI) were, respectively, 1.39 (1.10–1.77), 1.33 (1.04–1.69), and 1.44 (1.06–1.94). Atopy was associated with increased serum IL-6 and CRP; however, this did not mediate association between atopy and PEs. Inflammatory markers were not associated with later PEs.ConclusionChildhood atopic disorders increase the risk of psychotic experiences in adolescence. Follow-up of these individuals will be useful to determine the effect of atopy and inflammation on different trajectories of early-life PEs.     

Inflammatory biomarkers and emotional approach coping in men with prostate cancer

ObjectiveEmotion-regulating coping is associated with improvements in psychological and physical health outcomes. Yet in the context of prostate cancer-related stressors, limited research has characterized associations of emotion-regulating coping processes (emotional expression, emotional processing) and inflammatory processes that are related to disease risk. This investigation examined the relation of Emotional Approach Coping (EAC) with markers of inflammation to test the hypothesis that higher EAC scores at study entry (T1) would be associated with lower proinflammatory markers four months later (T2), specifically sTNF-RII, CRP, and IL-6.MethodsForty-one men (M age = 66.62 years; SD = 9.62) who had undergone radical prostatectomy or radiation therapy for localized prostate cancer within two years completed questionnaires, including assessments of EAC, at T1, and provided blood samples for immune assessments at T2.ResultsWhen controlling for relevant biobehavioral controls, emotional processing predicted lower IL-6 (B = −.66, p < .01), sTNF-RII (B = −.43, p < .05), and CRP (B = −.43, p < .10), whereas emotional expression was significantly associated with higher levels of sTNF-RII (B = .55, p < .05). Associations of emotional expression and IL-6 (B = .38, p < .10), and CRP (B = .44, p < .10) approached significance. Probing interactions of emotional processing and expression (though only approaching significance) suggested that expression of emotion is associated with higher inflammation (CRP and sTNF-RII) only in the context of low emotional processing.ConclusionsAttempts at emotion regulation via emotional processing appear to modulate inflammatory processes. Understanding, making meaning of, and working through emotional experience may be a promising target of intervention to reduce inflammation with potential effects on psychological and cancer outcomes in men with prostate cancer.     

C-reactive protein is elevated in schizophrenia

BackgroundIncreased levels of inflammatory markers have been reported in schizophrenia, but few studies have examined levels of high sensitivity C-reactive protein (CRP), a non-specific inflammatory marker.MethodsLevels of high sensitivity CRP were measured in individuals with schizophrenia, bipolar disorder, and non-psychiatric controls. Linear regression analyses were used to compare the CRP levels among the three groups adjusting for demographic and clinical variables. Logistic regression analyses were used to determine the odds ratios associated with elevated levels of CRP, defined as >=75th and 90th percentile in the controls.ResultsThe sample consisted of 715 individuals: 295 with schizophrenia, 192 with bipolar disorder, and 228 without a psychiatric disorder. The levels of CRP in the schizophrenia group, but not in the bipolar disorder group, were significantly increased compared to controls adjusting for age, gender, race, maternal education, smoking status, and Body Mass Index (BMI) (t = 3.78, p = < .001). The individuals with schizophrenia had significantly increased odds of having elevated levels of CRP relative to both the 75th and 90th percentile levels of the controls adjusting for the same covariates (OR 1.79, 95% CI 1.14, 2.82; p = .012; OR 2.76, 95% CI 1.58, 4.83, p = < .001). In the multivariate linear and logistic regression analyses, levels of CRP were also associated with BMI and female gender.ConclusionsIndividuals with schizophrenia may be at risk for the adverse health consequences associated with elevated CRP in the overall population. Trials of interventions directed at lowering the level of CRP and other inflammatory markers are indicated.     

Race/ethnicity moderates the relationship between depressive symptom severity and C-reactive protein: 2005–2010 NHANES data

Because few studies have examined depression facets or potential moderators of the depression–inflammation relationship, our aims were to determine whether particular depressive symptom clusters are more strongly associated with C-reactive protein (CRP) levels and whether race/ethnicity moderates these relationships. We examined data from 10,149 adults representative of the U.S. population (4858 non-Hispanic White, 1978 non-Hispanic Black, 2260 Mexican American, 1053 Other Hispanic) who participated in the cross-sectional National Health and Nutrition Examination Survey between 2005 and 2010. Depressive symptoms were assessed by the Patient Health Questionnaire-9, and high-sensitivity serum CRP was quantified by latex-enhanced nephelometry. Total (p < .001), somatic (p < .001), and nonsomatic (p = .001) depressive symptoms were each positively related to serum CRP in individual models. However, in the simultaneous model that included both symptom clusters, somatic symptoms (p < .001), but not nonsomatic symptoms (p = .98), remained associated with serum CRP. Evidence of moderation by race/ethnicity was also observed, as six of the nine depressive symptoms × race/ethnicity interactions were significant (ps < .05). Among non-Hispanic Whites, the pattern of results was identical to the full sample; only somatic symptoms (p < .001) remained related to serum CRP in the simultaneous model. No relationships between total, somatic, or nonsomatic symptoms and serum CRP were observed among the non-Hispanic Black, Mexican American, or Other Hispanic groups. Our findings indicate that the link between depressive symptoms and systemic inflammation may be due to the somatic symptoms of sleep disturbance, fatigue, appetite changes, and psychomotor retardation/agitation and may be strongest among non-Hispanic Whites.     

Effect of adenotonsillectomy on c-reactive protein levels in children with obstructive sleep apnea: A meta-analysis

ObjectiveChildren with obstructive sleep apnea syndrome (OSAS) have increased systemic inflammation, as assessed by c-reactive protein (CRP), and are at risk for substantial end-organ damage. Previous studies assessing the effect of adenotonsillectomy (T&A) on CRP in children with OSAS have yielded conflicting results. Therefore, the purpose of the current investigation was to perform a meta-analysis of the effect of T&A on CRP in children with OSAS and explore possible moderating factors.MethodsMultiple databases (PubMed, CINAHL, and Cochrane) were searched for relevant studies. Effective size was calculated with standardized mean differences (SMD) and analyzed with random-effects model. Moderators were examined with mixed-effects models.ResultsOverall, T&A significantly reduced CRP (SMD = −0.79, 95% CI −1.33 to −0.25). We found significant between-study heterogeneity (Cochran’s Q = 54.6, df = 7, p < 0.001; I2 = 90.7%, 95% CI 77.5–98.2%; and H2 = 10.7, 95% CI 4.5–55.7). We did not find evidence of publication bias or significant effects of tested moderators (study year, study size, age, gender, obesity, apnea–hypopnea index, oxygen nadir, pre-surgical CRP, follow-up duration).ConclusionsThe results of the current study indicate that T&A significantly reduces CRP levels in children with OSAS. Despite the presence of significant between-study heterogeneity, we did not identify any significant moderating factors.     

Circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) independently predict depressive symptom severity after 12 months in heart failure patients

Objective. To determine whether inflammatory markers prospectively predict depressive symptom severity 12 months later in heart failure (HF) patients. Methods. In 30 HF patients we assessed depressive symptom severity by the Beck depression inventory (BDI) at baseline as well as 12 months later. We measured circulating levels of the soluble intercellular adhesion molecule (sICAM)-1, the cytokine interleukin (IL)-6 and the acute phase protein C-reactive protein (CRP) at baseline assessment. Results. sICAM-1 (r = .38, p = .045) but not CRP or IL-6 correlated with BDI scores 12 months later. Hierarchical linear regression analysis revealed that independent of baseline BDI assessment, cardiovascular risk factors, indicators of HF disease severity, and medication intake, sICAM-1 significantly predicted BDI scores 12 months later. sICAM-1 independently explained between 7% (β = .26, p = .040) and 10% (β = .35, p = .045) of the total variance in BDI scores 12 months later. Conclusion. The findings from this exploratory analysis suggest that the adhesion molecule sICAM-1 is an independent predictor of depressive symptoms 12 months later in HF patients. Our prospective findings support the suggested role for inflammation in increasing future depressive symptom severity and extend this linkage for the first time to HF.     

Changes in salivary cortisol levels in pediatric patients with obstructive sleep apnea syndrome after adenotonsillectomy

ObjectiveObstructive sleep apnea syndrome (OSAS) activates the stress response system, including the hypothalamic–pituitary–adrenocortical (HPA) axis. The salivary cortisol, as an index of free circulating cortisol levels, may be used as a measure of HPA axis activity. We examined the change in the salivary cortisol level in pediatric OSAS patients before and after adenotonsillectomy (AT).MethodsForty-eight subjects from 80 subjects suspicious of having OSAS were diagnosed with OSAS by overnight PSG, 34 of 48 OSAS patients undergoing AT, and 13 of 34 OSAS patients were finally enrolled prospectively for this study. Before and three months after the AT, the saliva was collected at night before PSG (n-sCor) and in the early morning after PSG (m-sCor) for the measurements of the salivary cortisol level.ResultsChildren in the study population (n = 13) were divided into mild (1⩽ AHI <5, n = 5), moderate (5⩽ AHI <10, n = 3), and severe (AHI ⩾10, n = 5) OSAS groups. The mean preoperative AHI in the children was 14.7, and the mean postoperative AHI was 0.33. The percentage of children with AHI <1 after AT was 92.3%. Postoperative m-sCor, the difference of cortisol level (sub-sCor: m-sCor minus n-sCor), and the ratio of cortisol level (r-sCor: m-sCor/n-sCor) showed significant difference postoperatively.ConclusionsAT was associated with improvements in PSG and subjective symptoms in pediatric OSAS patients. In addition, these improvements were significantly related to normalization of salivary cortisol level after AT. Although further study on salivary cortisol levels needs to be done, the measurement of salivary cortisol level before and after AT may predict the outcome of AT as a treatment of OSAS.     

Sleep disturbance and longitudinal risk of inflammation: Moderating influences of social integration and social isolation in the Coronary Artery Risk Development in Young Adults (CARDIA) study

Both sleep disturbance and social isolation increase the risk for morbidity and mortality. Systemic inflammation is suspected as a potential mechanism of these associations. However, the complex relationships between sleep disturbance, social isolation, and inflammation have not been examined in a population-based longitudinal study. This study examined the longitudinal association between sleep disturbance and systemic inflammation, and the moderating effects of social isolation on this association. The CARDIA study is a population-based longitudinal study conducted in four US cities. Sleep disturbance – i.e., insomnia complaints and short sleep duration – was assessed in 2962 African–American and White adults at baseline (2000–2001, ages 33–45 years). Circulating C-reactive protein (CRP) was measured at baseline and follow-up (2005–2006). Interleukin-6 (IL-6) and subjective and objective social isolation (i.e., feelings of social isolation and social network size) were measured at follow-up. Sleep disturbance was a significant predictor of inflammation five years later after full adjustment for covariates (adjusted betas: 0.048, P = 0.012 for CRP; 0.047, P = 0.017 for IL-6). Further adjustment for baseline CRP revealed that sleep disturbance also impacted the longitudinal change in CRP levels over five years (adjusted beta: 0.044, P = 0.013). Subjective social isolation was a significant moderator of this association between sleep disturbance and CRP (adjusted beta 0.131, P = 0.002). Sleep disturbance was associated with heightened systemic inflammation in a general population over a five-year follow-up, and this association was significantly stronger in those who reported feelings of social isolation. Clinical interventions targeting sleep disturbances may be a potential avenue for reducing inflammation, particularly in individuals who feel socially isolated.     

An association between neuropeptide Y levels and leukocyte subsets in stress-exacerbated asthmatic mice

Neuropeptide Y (NPY) was recently proposed to be associated with stress and airway inflammation; however, this has rarely been studied in animal models of asthma. Twenty-four C57BL/6 mice were randomly divided into 3 groups of 8 each: naive control group, asthma group (with an established asthma model), and stressed asthma group (with established asthma and stress models). Bronchoalveolar lavage (BAL) fluid was collected for total cell counts using a hemocytometer and for cytological examinations by Wright stain. Differential inflammatory cell counts were performed to identify eosinophils, macrophages, neutrophils, and lymphocytes. NPY and corticosterone serum levels were determined with enzyme immunoassay kits. Stress was associated with increased airway inflammatory response, which was manifested by the accumulation of total leukocytes and eosinophils in the BAL fluid in comparison with the asthma and the control groups. The levels of NPY (p < 0.05) and corticosterone (p < 0.01) were elevated in the stressed asthma group in comparison with the control and asthma groups. The concentration of NPY and corticosterone positively correlated with the total leukocyte count (r = 0.892, p < 0.05 and r = 0.937, p < 0.01 respectively) and eosinophil numbers (r = 0.806, p = 0.053 and r = 0.885, p < 0.01 respectively).Stress may be associated with elevated peripheral NPY level, which was observed to be associated with exacerbated airway inflammation in asthmatic mice.     

Insufficient glucocorticoid signaling and elevated inflammation in coronary heart disease patients with comorbid depression

Coronary heart disease (CHD) and depression are very common and often co-existing disorders. In addition to psychological and social morbidity, depression exacerbates adverse cardiac outcomes in CHD patients. Inflammation has been proposed as one of the mechanisms involved in the association between these two debilitating diseases. Therefore, the present study aimed to evaluate inflammatory responses as well as to investigate the pathophysiological mechanisms underlying the putative inflammatory activation in CHD patients with and without depression, by assessing the function of two important biological factors regulating inflammation, the hypothalamus–pituitary–adrenal (HPA) axis and the glucocorticoid receptor (GR). Eighty-three CHD patients with (n = 28) and without (n = 55) comorbid depression were recruited from primary care services in South London. Depression status was assessed by means of Clinical Interview Schedule Revised for diagnosis of depression, and Beck Depression Inventory for the presence of depressive symptoms. Serum C-reactive protein (CRP), plasma vascular endothelial growth factor (VEGF), and plasma and salivary cortisol were measured using commercially available ELISA kits. Gene expression of GR and interleukin-6 (IL-6) were conducted via qPCR. GR sensitivity was evaluated in vitro in isolated peripheral blood mononuclear cells using the dexamethasone inhibition of lipopolysaccharide-stimulated IL-6 levels. Serum levels of kynurenine pathway metabolites were measured using high performance liquid chromatography. Our results show that CHD patients with depression had higher levels of CRP, IL-6 gene expression, and VEGF compared with CHD non-depressed, as well as lower plasma and saliva cortisol levels. The CHD depressed group also exhibited a reduction in GR expression and sensitivity. Finally, tryptophan levels were significantly lower in patients with depression, who also showed an increased kynurenine/tryptophan ratio. In conclusion, CHD patients with depression had elevated levels of inflammation in the context of HPA axis hypoactivity, GR resistance, and increased activation of the kynurenine pathway. Reduced cortisol bioavailability and attenuated glucocorticoid responsiveness due to decreased expression and sensitivity of GR may lead to insufficient glucocorticoid signaling and thus elevation of inflammation in these patients.     

A prospective study of C-reactive protein as a state marker in Cardiac Syndrome X

Cardiac Syndrome X (CSX), the presence of angina pectoris despite normal epicardial coronary arteries seen on invasive angiography, is known to be associated with an elevation of several inflammatory biomarkers, suggesting a possible role for inflammation in its pathogenesis. We sought to establish if C-reactive protein (CRP) levels varied with disease severity and so whether it is a state or trait marker. We studied 16 CSX patients with typical angina pectoris, normal coronary arteries and an electrically positive exercise stress test (EST) and 13 age- and sex-matched healthy controls (HC). CSX patients were followed up at a subsequent visit with repeated exercise stress testing and CRP measurement. We found that CRP levels were significantly higher in the CSX group compared to the HC (1.5 [0.8–4.5] v 0.8 [0.4–1.4] mg/L, p = 0.02). This elevation in CRP persisted throughout the study length. CRP correlated with time to symptoms on EST at enrolment and at the second visit (r = −0.690, df = 10, p = 0.013 and r = −0.899, df = 4, p = 0.015, respectively). At the follow-up visit, 50% of CSX patients developed electrically and symptomatically negative ESTs. The mean CRP of this group was significantly lower than that of the CSX patients with ongoing symptoms and positive ESTs (1.2 ± 0.2 v 2.8 ± 0.6 mg/L, p = 0.018) and did not differ significantly from that of healthy controls. CRP levels also dropped in patients whose symptoms improved while they increased in patients who became more symptomatic (p = 0.027). We conclude that the results of this small study support the concept of CSX being an inflammatory-mediated condition with CRP levels prospectively varying with functional measures of disease severity. This indicates that CRP is a state marker in CSX.     

The complementary role of high sensitivity C-reactive protein in the diagnosis and severity assessment of autism

C-reactive protein (CRP) is a beneficial diagnostic test for the evaluation of inflammatory response. Extremely low levels of CRP can be detected using high-sensitivity CRP (hs-CRP) test. A considerable body of evidence has demonstrated that inflammatory response has an important role in the pathophysiology of autism. In this study, we evaluated and compared hs-CRP levels between autistic and intellectually normal individuals. Clinical data of 39 autistic and 30 age-matched intellectually normal individuals (control group) were recorded. Patients were divided into two groups (mild-to-moderate and severe) according to childhood autism rating scale. Then serum hs-CRP concentrations were measured and compared between two groups. Also, the correlation between hs-CRP concentration and the severity of autism was determined. The mean concentration of hs-CRP in children with autism (540.1 ± 1125.5 ng/ml) was significantly (P < 0.0001) higher than control group (1.3 ± 1.0 ng/ml). In severe autism, the mean level of hs-CRP (985.1 ± 1432.1 ng/ml) was significantly (P = 0.008) higher than the mean level of hs-CRP in patients with mild-to-moderate autism (147.1 ± 60.4 ng/ml). There was a positive correlation between hs-CRP concentration and autism severity (r = 0.34; P = 0.039). These findings affirm the role of inflammation in autism.