Early childhood risk exposures and inflammation in early adolescence.

There is now reliable evidence that early psychosocial stress exposures are associated with behavioral health in children; the degree to which these same kinds of stress exposures predict physical health outcomes is not yet clear. We investigated the links between economic adversity, family and caregiving stress in early childhood and several markers of immune function in early adolescence. The sample is derived from the Family Life Project, a prospective longitudinal study of at-risk families. Socio-demographic and psychosocial risks have been assessed at regular intervals since the children were first assessed at 2 months of age. When the children were early adolescents, we conducted an in-depth health assessment of a subsample of families; blood samples were collected from venipuncture for interleukin(IL)-6, Tumor Necrosis Factor (TNF)-alpha, and C-reactive protein (CRP), as well as glucocorticoid resistance. Results indicated limited but reliable evidence of an association between early risk exposure and inflammation in adolescence. Specifically, caregiver depressive symptoms in early childhood predicted elevated CRP almost a decade later, and the prediction was significant after accounting for multiple covariates such as socio-economic adversity, health behaviors and body mass index. Our findings provide strong but limited evidence that early stress exposures may be associated with inflammation, suggesting one mechanism linking early stress exposure to compromised behavioral and somatic health.

Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy.

BACKGROUND: Cancer-related cognitive impairment (CRCI) is often related to chemotherapy. Increased chronic inflammation is believed to play a key role in the development of CRCI related to chemotherapy but studies assessing this hypothesis specifically in patients receiving chemotherapy are rare. METHODS: We assessed several cognitive domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in twenty-two breast cancer patients currently receiving chemotherapy. We also measured inflammatory cytokine and receptor (MCP-1, TNF-α, sTNFRI, sTNFRII) concentrations in patient sera using Luminex assays. These concentrations were log-transformed to obtain a normal distribution. Associations between log-transformed cytokines and cognition were evaluated using Pearson correlations and linear regression, taking into account relevant covariates. RESULTS: Increased concentrations of sTNFRI and sTNFRII were associated with poorer performance on the CANTAB Delayed Matching to Sample (DMS, tests visual memory). Increasing sTNFRI levels were negatively correlated with DMS percent correct (r=-0.47, p=0.029) and DMS percent correct after a 12 second (s) delay (r=-0.65, p=0.001). Increasing levels of sTNFRII negatively correlated with DMS percent correct after 12s delay (r=-0.57, p=0.006). After controlling for relevant demographic (i.e. age, education) and clinical variables (i.e. disease stage, regimen type), we found that increased sTNFRI remained significantly related to decline on the DMS at the 12s delay (p=0.018). CONCLUSION: This preliminary study shows a significant association between higher sTNFRI and lower scores on the short-term visual memory delayed match to sample test in breast cancer patients receiving chemotherapy, supporting the hypothesis that sTNFRI is involved in CRCI.

Social Relationships and Inflammatory Markers in the MIDUS Cohort: The Role of Age and Gender Differences.

OBJECTIVE: To better understand age and gender differences in associations of social relationships with chronic inflammation. METHOD: Using a sample of middle-aged and older adults ( N = 963) from the Midlife Development in the United States (MIDUS) biomarker project, we examined interactions of age and gender with structural and functional social network measures in predicting interleukin-6 (IL-6) and C-reactive protein (CRP). RESULTS: Significant interactions involving age and gender showed that social support was associated with lower IL-6 in older women, whereas perceived positive relationships and social integration were related to lower IL-6 in both men and women of advanced age. Functional measures were associated with higher CRP in both men and women after adjustment for health conditions and behaviors, with some further variation by age. DISCUSSION: Greater social support may be related to lower IL-6 in older women. Further research is needed to understand observed associations of social support with higher CRP.

Lifetime Exposure to Intimate Partner Violence and Proinflammatory Cytokine Levels Across the Perinatal Period.

BACKGROUND: Intimate partner violence (IPV) is a public health concern, affecting one-third of US women. Prior research suggests an association between exposure to IPV and poor maternal perinatal health, but the underlying biological correlates are not well understood. This study examined the relationship between exposure to IPV and proinflammatory cytokine levels, a candidate mechanism accounting for poor psychiatric and obstetric outcomes, across the perinatal period. MATERIALS AND METHODS: Data were obtained from a prospective, longitudinal cohort study of 171 women receiving obstetrical care from a hospital-based practice serving a predominantly low-income minority population. Participants completed questionnaires on IPV exposure, psychiatric symptoms, and psychosocial and obstetric factors and provided blood samples at 18 and 32 weeks of gestation and 6 weeks and 6 months postpartum. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were assayed via enzyme-linked immunosorbent assay. RESULTS: Thirty-five (20.5%) women reported lifetime exposure to IPV and 7 (4.1%) reported being physically hurt in the preceding 12 months (4 while pregnant). Lifetime exposure to IPV was associated with increased likelihood of experiencing perinatal depression and smoking during pregnancy. Women with a history of IPV had significantly higher levels of TNF-α at 18 weeks (z = -2.29, p < 0.05), but significantly smaller changes in levels of IL-6 (ß = -0.36, p = 0.04) across time. CONCLUSION: Lifetime exposure to IPV was associated with a range of adverse mental health outcomes and may affect proinflammatory cytokine levels in pregnancy.

Circulating endocannabinoids during hematopoietic stem cell transplantation: A pilot study.

OBJECTIVE: Hematopoietic stem cell transplantation (HCT) is a stressful and rigorous medical procedure involving significant emotional and immune challenges. The endocannabinoid (eCB) signaling system is involved in regulation of both the immune system and emotional reactivity, yet little is known about its function during HCT. We investigated the role of the eCB signaling system in a group of HCT recipients. METHODS: A total of 19 HCT recipients were enrolled and provided psychosocial data and blood samples at three peri-transplant time points: prior to transplant, hospital discharge, and approximately 100 days post-transplant. Psychosocial factors, inflammatory molecules, and the eCBs were determined and assessed for changes over this period and association with each other. RESULTS: HCT recipients demonstrated significant changes over the peri- transplant period in inflammatory molecules and psychosocial functioning, but not in circulating concentrations of the eCBs. Associations among these variables were most likely to be present pre-transplant and least likely to be present immediately post-transplant, with depressive symptoms and inflammation most significantly associated. The eCB 2-arachidonoylglycerol (2-AG) was significantly, positively associated with both interleukin (IL)-6 and C-reactive protein (CRP) and negatively associated with depressive symptoms. CONCLUSIONS: The eCB signaling system may have alternative sources and regulatory mechanisms in addition to the immune system. Given the significant associations with inflammatory molecules and depressive symptoms in the peri- transplant period, it is important to better understand this system and its potential implications in the setting of complex and stressful medical procedures such as HCT.

Mindfulness-based stress reduction to enhance psychological functioning and improve inflammatory biomarkers in trauma-exposed women: A pilot study.

This study examined the effects of a mindfulness-based stress reduction (MBSR) program on psychological functioning and inflammatory biomarkers in women with histories of interpersonal trauma. The 8-week MBSR program was conducted at a community-based health center and participants (N = 50) completed several measures of psychological functioning at study entry as well as 4 weeks, 8 weeks, and 12 weeks later. Inflammatory biomarkers were assayed from blood collected at each assessment. A series of linear mixed-model analyses were conducted to measure the effect of attendance and time on the dependent variables. Time was associated with significant decreases in perceived stress, depression, trait and state anxiety, emotion dysregulation, and posttraumatic stress symptoms, as well as increases in mindfulness. Session attendance was associated with significant decreases in interleukin (IL)-6 levels. This pilot study demonstrated the potential beneficial effects of MBSR on psychological functioning and the inflammatory biomarker IL-6 among trauma-exposed and primarily low-income women. Decreases in inflammation have implications for this population, as interpersonal trauma can instigate chronic physiological dysregulation, heightened morbidity, and premature death. This study's preliminary results support efforts to investigate biological remediation with behavioral interventions in vulnerable populations.

Peri-transplant psychosocial factors and neutrophil recovery following hematopoietic stem cell transplantation.

OBJECTIVE: Multiple psychosocial factors appear to affect cancer progression in various populations; however, research investigating the relationship between psychosocial factors and outcomes following hematopoietic stem cell transplantation (HCT) is scarce. Subject to adverse immunological and psychological conditions, HCT patients may be especially vulnerable to psychosomatic health sequelae; therefore, we studied whether optimism and anxiety influence the pertinent clinical outcome of days to neutrophil engraftment (DTE). METHOD: 54 adults undergoing either autologous or allogeneic HCT completed self-report questionnaires measuring optimism and anxiety. We assessed the association between these psychosocial variables and DTE. RESULTS: Greater optimism and less anxiety were associated with the favorable outcome of fewer DTE in autologous HCT recipients, though this relationship was no longer significant when reducing the sample size to only subjects who filled out their baseline survey by the time of engraftment. CONCLUSION: Our findings are suggestive that optimism and anxiety may be associated with time to neutrophil recovery in autologous, but not allogeneic, adult HCT recipients. Further investigation in larger, more homogeneous subjects with consistent baseline sampling is warranted.

Depressive symptoms and proinflammatory cytokines across the perinatal period in African American women.

BACKGROUND: Comparatively few studies have examined the biological mechanisms that may underlie the reported racial disparities in antenatal and postpartum depression. OBJECTIVE: To examine the associations among race, depressive symptoms and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α across the perinatal period in a diverse sample of healthy pregnant women at elevated psychosocial risk. METHODS: 171 subjects were enrolled. Women were interviewed and blood samples drawn at 18 and 32 weeks gestation and 6 weeks and 6 months postpartum. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale. Serum levels of IL-6 and TNF-α were assayed using high sensitivity enzyme-linked immunosorbent assay kits. RESULTS: Compared with non-African American (AA) women, AA women had significantly higher levels of IL-6 (est. diff = 0.521, p = 0.02, confidence interval (CI): 0.088-0.954) but not TNF-α across all time points (est. diff = -0.060, p = 0.80, CI: -0.517 to 0.397). IL-6 was not associated with depressive symptoms but differences in IL-6 were accounted for by greater Body Mass Index in AA women. CONCLUSIONS: Compared with non-AA women, AA women entered pregnancy with elevated inflammatory cytokine levels that persisted across the perinatal period. This group difference in inflammation did not suggest increased risk for depression, but suggests other implications for long-term health.

Psychosocial factors and hematopoietic stem cell transplantation: potential biobehavioral pathways.

While psychosocial factors are known to affect cancer progression via biobehavioral pathways in many patient populations, these relationships remain largely unexplored in hematopoietic stem cell transplant (HCT) patients. The purpose of this paper is to critically review the literature regarding psychosocial and endocrine/immune aspects of HCT, with an emphasis on exploring pathways that may mediate the associations between psychosocial factors and disease outcomes. These include the roles of catecholamines, glucocorticoids, inflammation, vascular endothelial growth factor (VEGF), immune reconstitution and infectious susceptibility, as well as the new opportunities available in genomics research. We also discuss the implications for potential immunomodulating psychosocial interventions. Elucidating the biological pathways that account for the associations between psychosocial factors and clinical course could ultimately lead to improved outcomes for this psychologically and immunologically vulnerable population.

Depressive symptoms, pain, chronic medical morbidity, and interleukin-6 among primary care patients.

OBJECTIVE: Pain, chronic medical morbidity, and depression are highly prevalent problems that frequently co-occur in primary care. Elevated levels of inflammatory markers are linked with all three of these conditions and may play an important role in patients' comorbidities. The current study aimed to examine if the associations among pain, chronic medical morbidity, and the inflammatory marker interleukin (IL)-6 are dependent on depression status in primary care patients. SETTING, SUBJECTS, AND OUTCOME MEASURES: Primary care patients (N = 106) aged 40 and older were assessed for pain (36-item Medical Outcomes Study Survey Form), chronic medical morbidity (checklist of chronic health conditions), and depressive symptoms (Center for Epidemiologic Studies Depression Scale), and provided a blood sample for the measurement of serum IL-6. RESULTS: Among patients with elevated depressive symptoms, higher IL-6 levels were associated with both greater pain and greater chronic medical comorbidity. IL-6 was unrelated to pain or chronic medical comorbidity among patients without clinically significant depressive symptoms. In mediation analyses, chronic medical morbidity did not mediate the association between IL-6 and pain, and depression severity and pain remained independently associated after adjustment for chronic medical comorbidity. CONCLUSIONS: Depression may increase primary care patients' vulnerability to pain and elevated levels of inflammatory markers such as IL-6.

Toward identifying the effects of the specific components of Mindfulness-Based Stress Reduction on biologic and emotional outcomes among older adults.

OBJECTIVES: The objectives of this study were to examine the effects of specific Mindfulness-Based Stress Reduction (MBSR) activities (yoga, sitting and informal meditation, body scan) on immune function, circulating insulin-like growth factor (IGF)-1 concentrations, and positive affect among older adults. DESIGN: The study design comprised longitudinal analyses of data from subjects in an 8-week MBSR program. SETTING: The study was conducted at a University-affiliated health center. SUBJECTS: This study involved 100 community-dwelling older adults. Inclusion criteria were as follows: ≥65 years of age and English-speaking. INTERVENTION: This was an 8-week MBSR program. OUTCOME MEASURES: Interleukin (IL)-6 and IGF-1 levels were assayed from blood collected at postintervention assessments. Participants were immunized postintervention with keyhole limpet hemocyanin (KLH), and immunoglobulin (Ig)M and IgG KLH-specific antibody responses were measured prior to immunization as well as 3 weeks and 24 weeks postintervention. Participants completed a 10-item measure of positive affect at study entry and postintervention. RESULTS: Participants maintained weekly practice logs documenting participation in yoga, sitting meditation, informal meditation, and body scan. More practice of yoga was associated with higher post-treatment IGF-1 levels and greater improvement in positive affect from study entry to postintervention. Sitting meditation was positively associated with post-treatment IGF-1. Greater use of body scanning was associated with reduced antigen-specific IgM and IgG 3 weeks postintervention but not 24 weeks. No associations were found between MBSR activities and IL-6 levels. CONCLUSIONS: Practice of MBSR activities, particularly yoga, could provide benefits for specific aspects of physiologic function and positive affect. Changes in adaptive immunity in older adult MBSR practitioners warrant further study.

Elevated levels of interleukin 6 and C-reactive protein associated with cognitive impairment in heart failure.

There is abundant evidence on inflammatory mechanisms in heart failure (HF) that are used for prognostication of the disease; however, data are lacking regarding the association between elevated cytokines, C-reactive protein (CRP), and cognition in HF. A cross-sectional pilot study of 38 patients with HF, aged 62 years (standard deviation± 9 years), predominantly men (68%) and Caucasian (79%) were screened for cognitive function using the Montreal Cognitive Assessment (MoCA). The study aimed to examine cognitive scores on MoCA with cytokines, interleukin 6 [IL-6] and tumor necrosis factor α [TNF-α], and CRP as indicators of early cognitive changes in HF. The result showed no direct correlation between cardiac variables and the MoCA score. The MoCA score, however, was inversely associated with IL-6 (r=-0.53, P=.001) and CRP (r=-0.34, P=.04), with no association to TNF-α. Regression analysis on the MoCA score and log-transformed IL-6 accounted for an additional 11% variation and remained statistically significant (P=.008) after controlling for covariates of education, living arrangements, and loneliness. The large effect size (R(2) =0.87) found in this pilot study provides rationale for a larger exploratory study to examine associations between cognitive function, cytokines, and CRP levels and help design future intervention studies.

Big 5 personality traits and interleukin-6: evidence for "healthy Neuroticism" in a US population sample.

The current study investigated if the Big 5 personality traits predicted interleukin-6 (IL-6) levels in a national sample over the course of 5years. In addition, interactions among the Big 5 were tested to provide a more accurate understanding of how personality traits may influence an inflammatory biomarker. Data included 1054 participants in the Midlife Development in the U.S. (MIDUS) biomarkers subproject. The Big 5 personality traits were assessed in 2005-2006 as part of the main MIDUS survey. Medication use, comorbid conditions, smoking behavior, alcohol use, body mass index, and serum levels of IL-6 were assessed in 2005-2009 as part of the biomarkers subproject. Linear regression analyses examined personality associations with IL-6. A significant Conscientiousness*Neuroticism interaction revealed that those high in both Conscientiousness and Neuroticism had lower circulating IL-6 levels than people with all other configurations of Conscientiousness and Neuroticism. Adjustment for health behaviors diminished the magnitude of this association but did not eliminate it, suggesting that lower comorbid conditions and obesity may partly explain the lower inflammation of those high in both Conscientiousness and Neuroticism. Our findings suggest, consistent with prior speculation, that average to higher levels of Neuroticism can in some cases be associated with health benefits - in this case when it is accompanied by high Conscientiousness. Using personality to identify those at risk may lead to greater personalization in the prevention and remediation of chronic inflammation.

Sleep disturbance and older adults' inflammatory responses to acute stress.

OBJECTIVES: Poor sleep diminishes mental and physical health. The objective of this study was to examine associations between sleep disturbance and interleukin-6 (IL-6) responses to acute mental stress in older adults. DESIGN: Observational study of community-dwelling, healthy older adults. SETTING: Participants completed the study in a clinical research laboratory of a mid-sized university. PARTICIPANTS: Generally healthy, community-dwelling men and women age 50 and older. MEASUREMENTS: IL-6 and negative affect at rest and following a series of challenging cognitive tests; sleep quality; depressive symptoms; perceived stress; loneliness. RESULTS: Participants categorized as poor sleepers on the basis of Pittsburgh Sleep Quality Index scores had significantly larger IL-6 responses to the cognitive stressors than good sleepers. The association between poor sleep and heightened IL-6 response to acute stress was not explained by other psychosocial factors previously linked to immune dysregulation, including depressive symptoms, perceived stress, and loneliness. CONCLUSIONS: Findings add to the growing evidence for poor sleep as an independent risk factor for poor mental and physical health. Older adults may be particularly vulnerable to effects of sleep disturbance due to significant age-related changes in both sleep and inflammatory regulation.

Associations among depression, perceived self-efficacy, and immune function and health in preadolescent children.

Experimental animal studies and adult research consistently show that stress exposure and/or psychological symptoms are associated with poorer health and immune functioning. The application to children is not yet clear, however, and we lack developmental models for studies in this area. The objective of this paper was to test the hypothesis that self-reported self-efficacy and depression, two markers of psychological well-being in children, would predict immunity and rate of illnesses. The data are based on a prospective study of 141 healthy, normally developing children aged 7-13 years who were recruited from an ambulatory pediatric setting. Children completed self-efficacy and depression measures and had blood obtained for IL-6 plasma levels and natural killer cell functional assays on three occasions, 6 months apart. Parents maintained weekly child illness diaries over 1 year using a thermometer to record fever. Parent psychiatric symptoms and income were used as covariates. Results indicated that, across the three occasions of measurement collected over the 1-year period, higher perceived self-efficacy was significantly associated with lower plasma interleukin 6 concentrations. There was no overall main effect of depressive symptoms on immune measures; however, for older girls, higher depression was associated with elevated natural killer cell cytotoxicity and an increased rate of total illnesses and febrile illnesses. The findings provide some of the first evidence that psychological processes are associated with immunity and health in a normally developing sample of preadolescents. Furthermore, the pattern of results suggests a modified model of a link between psychological well-being and immunological processes in children. These results build on and expand research on the notion of allostatic load and develop a groundwork for developmental studies in this area.

Psychiatric symptoms and proinflammatory cytokines in pregnancy.

OBJECTIVE: Clinical studies suggest that psychiatric symptoms, particularly depression, anxiety, and trauma, may be associated with inflammation, as indexed by proinflammatory cytokines. Such a link may be especially significant in pregnancy and may shed additional light on the etiology of perinatal mood disorders. METHODS: We prospectively observed 145 women selected from a community obstetric clinic serving a primarily low-income, high-psychosocial risk population. Women without evidence of medical high-risk pregnancies were screened (including psychiatric and trauma histories) and then assessed in detail (e.g., mood symptoms) at approximately 18 and 32 weeks' gestation. Blood was drawn to measure key proinflammatory markers, interleukin 6 and tumor necrosis factor α (TNF-α). Data on pregnancy and obstetric outcome were derived from medical records. RESULTS: There was considerable stability of cytokine levels within individuals and a significant mean increase across pregnancy observed for interleukin 6 (p < .001) and TNF-α (p < .001). History of trauma was associated with significantly elevated TNF-α levels (F(1,135) = 4.43, p < .05), controlling for psychosocial and obstetric covariates. In contrast, elevated measures of depression and anxiety were unrelated to proinflammatory cytokines (p > .1). Exploratory analyses indicated that neither psychiatric symptoms nor proinflammatory cytokines predicted birth weight, gestational age, or obstetric complications. CONCLUSIONS: These findings suggest that antecedent trauma may be associated with persistently elevated TNF-α levels during pregnancy. The evidence that a generalized proinflammatory state was associated with symptoms of depression or anxiety in pregnant women was not found.

Moderating effects of moderate-intensity physical activity in the relationship between depressive symptoms and interleukin-6 in primary care patients.

OBJECTIVE: To determine whether the relationship between interleukin (IL)-6 and depressive symptoms is moderated by participation in moderate-intensity physical activity in a sample of primary care patients. Elevated inflammation has been associated with a number of poor health outcomes. Depressive symptoms may be related to higher levels of the inflammatory marker IL-6; however, previous findings are inconsistent, possibly due to unidentified moderating factors. METHODS: A total of 107 participants, aged ≥ 40 years, were recruited in Rochester, New York, in 2006 to 2007. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression Scale-Revised, participation in moderate-intensity physical activity was measured using a modified version of the Community Health Activities Model Program for Seniors Activity Questionnaire for Older Adults, and serum IL-6 concentrations were determined using standard enzyme-linked immunosorbent assay protocols and high-sensitivity, anti-cytokine antibody pairs. A hierarchical multiple regression analysis was conducted. RESULTS: The correlation between IL-6 and depressive symptoms was nonsignificant (r = .086, p = .40). The association between IL-6 and depressive symptoms was moderated by participation in moderate-intensity physical activity (p = .02). Among those who did not engage in moderate-intensity physical activity, higher levels of depressive symptoms were significantly associated with higher levels of IL-6 (r = .28, p = .05), whereas this association was not significant among those who did participate in moderate-intensity physical activity (r = -.13, p = .38). CONCLUSION: Participation in moderate-intensity physical activity may buffer the risk of higher inflammation often associated with higher levels of depressive symptoms.

Openness and conscientiousness predict 34-week patterns of Interleukin-6 in older persons.

Studies have indicated that personality may be associated with inflammatory markers such as Interleukin (IL)-6. One pathway between personality and IL-6 may be health behaviors and conditions resulting in inflammation, while an alternate pathway involves activation of stress-response systems. In a clinical trial sample of 200 older adults, we examined associations between personality traits at baseline and three measures of IL-6 spanning 34 weeks of follow-up. Results indicate that IL-6 remained very stable over time, and that higher Conscientiousness and Openness were associated with lower IL-6 across the entire 34 week period. Goal striving was the active subcomponent of Conscientiousness, while aesthetic interests was the active subcomponent of Openness in IL-6 associations. Common health behaviors and chronic illness accounted for only a portion of these effects, suggesting that other behavioral and/or physiological processes may also predispose some persons to inflammation. Personality phenotype may provide useful prognostic information for inflammation. Older adults lower in Conscientiousness and Openness constitute a target population for anti-inflammatory interventions. Openness and Conscientiousness predicts 32-week patterns of Interleukin-6 in older persons.

History of sudden unexpected loss is associated with elevated interleukin-6 and decreased insulin-like growth factor-1 in women in an urban primary care setting.

OBJECTIVE: To investigate the hypothesis that a history of sudden unexpected loss including number of losses and type of loss (death due to unnatural versus natural causes) would be associated with the magnitude of dysregulation. The sudden unexpected death of a loved one confers risk of morbidity and mortality, perhaps due to dysregulation in the immune/inflammatory and endocrine systems. METHODS: Female primary care patients aged >or=40 years (n = 75) completed questionnaires, a clinical interview, and a blood draw. Interleukin (IL)-6 and insulin-like growth factor (IGF)-1 were assayed, using standard enzyme-linked immunosorbent assay protocols and anticytokine antibody pairs. RESULTS: History of sudden loss was positively associated with IL-6 (mean = 4.07 pg/mL; log(10) values, B = 0.314, p = .009) and negatively associated with IGF-1 (mean = 97.05 ng/mL; B = -0.277, p = .023). A linear relationship parsimoniously captured the association between ordered categories of lifetime loss (0, 1, 2-5, 5+) and increases in log(10) IL-6 (B = 0.107, p = .005) and decreases in IGF-1 (B = -0.116, p = .005). Adjusting for illness burden, depressive symptom severity, and obesity did not change the observed associations. The hypothesized effect of type of loss was not supported. CONCLUSIONS: These preliminary findings encourage further investigations to elucidate pathways from sudden unexpected loss to biomarker changes that increase risk for morbidity and mortality.

Gender, race/ethnicity, personality, and interleukin-6 in urban primary care patients.

Gender, race/ethnicity, and personality are markers of significant psychosocial and biological variability. Each may have implications for allostatic load and resulting inflammatory processes, yet findings have been largely mixed. We investigated whether women, minorities, and those higher in Neuroticism and lower in Extraversion were at risk for elevated circulating levels of the pro-inflammatory cytokine interleukin (IL)-6 in a sample of 103 middle aged and older urban primary care patients. Regression analyses controlling for age, education, current depression levels, and chronic medical conditions revealed that women, minorities, and individuals lower in Extraversion had higher circulating levels of IL-6. Analyses of more specific personality traits revealed that the sociability and positive emotions components of Extraversion were unassociated with IL-6, but the activity facet-reflecting dispositional vigor and energy-was robustly associated with IL-6. The difference between high (+1 Standard Deviation (SD)) and low (-1 SD) trait activity was sufficient to shift IL-6 levels beyond a previously established high risk cut-point in both white and minority women. These findings suggest that while broad group differences between genders and races/ethnicities exist, personality represents an important source of individual differences in inflammation within groups. Future work should examine to what extent IL-6 levels are linked to temperament or genetic activity levels vs. physical activity itself, and whether IL-6 levels may be reduced by boosting regular activity levels in demographic segments such as women and minorities who appear susceptible to greater inflammation.