Neha A. John-Henderson

Positive Affect and Markers of Inflammation: Discrete Positive Emotions Predict Lower Levels of Inflammatory Cytokines

Negative emotions are reliably associated with poorer health (e.g., Kiecolt-Glaser, McGuire, Robles, & Glaser, 2002), but only recently has research begun to acknowledge the important role of positive emotions for our physical health (Fredrickson, 2003). We examine the link between dispositional positive affect and one potential biological pathway between positive emotions and health-proinflammatory cytokines, specifically levels of interleukin-6 (IL-6). We hypothesized that greater trait positive affect would be associated with lower levels of IL-6 in a healthy sample. We found support for this hypothesis across two studies. We also explored the relationship between discrete positive emotions and IL-6 levels, finding that awe, measured in two different ways, was the strongest predictor of lower levels of proinflammatory cytokines. These effects held when controlling for relevant personality and health variables. This work suggests a potential biological pathway between positive emotions and health through proinflammatory cytokines.

The effects of acute psychological stress on circulating and stimulated inflammatory markers: A systematic review and meta-analysis.

Inflammatory reactivity to acute laboratory stress is thought to reflect individual differences in responsivity to environmental stressors and may confer future health risk. To characterize this response, we conducted a meta-analysis of 34 studies that measured circulating inflammatory markers and 15 studies that measured stimulated production of inflammatory markers before and after exposure to laboratory challenge. Results showed significant stress-related increases in circulating interleukin (IL)-1β (d=0.66, p<0.001), IL-6 (d=0.35, p<0.001), IL-10 (d=0.69, p<0.001), and tumor necrosis factor(TNF)-α (d=0.28, p<0.001), but not IL-1ra, IL-2, interferon-γ, or C-reactive protein. There were sufficient data to assess the time course of IL-6, IL-1β, and TNF-α reactivity. IL-6 increased from baseline to measures taken 40-50, 60-75, 90, and 120min following stress, with the largest effect at 90min post-stress (d=0.70, p<0.001). IL-1β increased from baseline to 20-30, 40-50, and 60-70min following stress, with the largest effect between 40 and 50min post-stress (d=0.73, p=0.02). For TNF-α, there was a significant increase from baseline to 31-50min post stress (d=0.44, p=0.01), but not at later times. There was no difference in magnitude of IL-6 reactivity as a function of type of stress (social-evaluative versus other). For stimulated inflammatory markers, results showed stress-related increases in IL-1β when measured 20-120min post-stress (d=1.09, p<0.001), and in IL-4 and interferon-γ when measured 0-10min post stressor (d=-0.42, p<0.001 and d=0.47, p<0.001). These results extend findings from a prior meta-analysis (Steptoe et al., 2007) to show reliable increases in circulating IL-6, IL-1β, IL-10 and TNF-α and stimulated IL-1β, IL-4 and interferon-γ in response to acute stress. It is possible that these responses contribute to associations between exposure to life challenges and vulnerability to inflammatory disease.

Performance and Inflammation Outcomes are Predicted by Different Facets of SES Under Stereotype Threat

We experimentally tested whether negative stereotypes linked to lower socioeconomic status (SES), in addition to impairing academic performance (Croizet & Claire, 1998), instigate inflammation processes that are implicated in numerous disease processes. In Study 1, verbal test performance and activation of inflammation processes (measured by levels of an inflammatory protein, Interleukin-6 [IL-6]) varied as a function of SES and test framing (i.e., diagnostic vs. nondiagnostic of intellectual ability), with low SES students underperforming and exhibiting greater IL-6 production in the “diagnostic” condition. In Study 2, students expected their verbal exam performance to be compared to peers of higher or lower SES. Low SES students in the upward comparison condition displayed the greatest inflammatory response and worst test performance. Across both studies, different facets of SES predicted vulnerability to negative outcomes, such that low early life SES predicted heightened inflammation responses, while low current SES predicted impaired academic performance.

The social environment and IL-6 in rats and humans

Inflammatory cytokine levels predict a wide range of human diseases including depression, cardiovascular disease, type 2 diabetes, autoimmune disease, general morbidity, and mortality. Stress and social experiences throughout the lifecourse have been associated with inflammatory processes. We conducted studies in humans and laboratory rats to examine the effect of early life experience and adult social position in predicting IL-6 levels. Human participants reported family homeownership during their childhood and current subjective social status. Interleukin-6 (IL-6) was measured from oral mucosal transudate. Rats were housed in groups of three, matched for quality of maternal care received. Social status was assessed via competition for resources, and plasma IL-6 was assessed in adulthood. In both humans and rats, we identified an interaction effect; early social experience moderated the effect of adult social status on IL-6 levels. Rats that experienced low levels of maternal care and people with low childhood socioeconomic status represented both the highest and lowest levels of IL-6 in adulthood, depending on their social status as young adults. The predicted interaction held for non-Hispanic people, but did not occur among Hispanic individuals. Adversity early in life may not have a monotonically negative effect on adult health, but may alter biological sensitivity to later social experiences.

Socioeconomic Status and Social Support Social Support Reduces Inflammatory Reactivity for Individuals Whose Early-Life Socioeconomic Status Was Low

Low socioeconomic status (SES) during childhood confers risk for adverse health in adulthood. Accumulating evidence suggests that this may be due, in part, to the association between lower childhood SES and higher levels of pro-inflammatory cytokines. Drawing from literature showing that low childhood SES predicts exaggerated physiological reactivity to stressors and that lower SES is associated with a more communal, socially attuned orientation, we hypothesized that inflammatory reactivity would be more greatly affected by cues of social support among individuals whose childhood SES was low than among those whose childhood SES was high. In two studies, we found that individuals with lower subjective childhood SES exhibited greater reductions in pro-inflammatory cytokine reactivity to a stressor in the presence of a supportive figure (relative to conditions with an unsupportive or neutral figure). These effects were independent of current SES. This work helps illuminate SES-based differences in inflammatory reactivity to stressors, particularly among individuals whose childhood SES was low.

Wealth, Health, and the Moderating Role of Implicit Social Class Bias

BackgroundSubjective social status (captured by the MacArthur Scale of Subjective Social Status) is in many cases a stronger predictor of health outcomes than objective socioeconomic status (SES).PurposeThe study aims to test whether implicit beliefs about social class moderate the relationship between subjective social status and inflammation.MethodsWe measured implicit social class bias, subjective social status, SES, and baseline levels of interleukin-6 (IL-6), a marker of inflammation, in 209 healthy adults.ResultsImplicit social class bias significantly moderated the relationship between subjective social status and levels of IL-6, with a stronger implicit association between the concepts “lower class” and “bad” predicting greater levels of IL-6.ConclusionsImplicit social class bias moderates the relationship between subjective social status and health outcomes via regulation of levels of the inflammatory cytokine IL-6. High implicit social class bias, particularly when one perceives oneself as having low social standing, may increase vulnerability to inflammatory processes.

Childhood Socioeconomic Status and the Occurrence of Recent Negative Life Events as Predictors of Circulating and Stimulated Levels of Interleukin-6.

Objectives Evidence supports an inverse association of childhood socioeconomic status (SES) with systemic inflammation in adulthood. However, it remains to be determined whether this association is dependent on exposure to stressful life experiences. Methods We predicted that the combination of a high number of recent negative life events and low childhood SES would be associated with the highest levels of both circulating interleukin (IL)-6 and lipopolysaccharide-stimulated production of IL-6. We tested this prediction among a community sample of 459 adults (47% male, mean [standard deviation] age = 42.8 [7.3] years). Results Inverse associations were found between childhood and adult SES indices with circulating IL-6 levels (r values between −0.07 and −0.16, p < .05) but not stimulated IL-6 levels (r values between −0.007 and 0.07, p > .05). The number of recent negative life events (mean [standard deviation] = 2.43 [2.34]) was not significantly related to subjective childhood SES and other SES indices (r values < 0.06, p > .10). Multivariate linear regression analyses revealed a significant association between the interaction of subjective childhood SES and recent negative life events and circulating IL-6 (&bgr; = −0.09, t(404) = −1.98, p = .049) and a marginally significant association with stimulated levels of IL-6 (&bgr; = −0.10, t(365) = −1.94, p = .054), whereas these covariate-adjusted models revealed no main effects for subjective SES or recent negative life events. Conclusions The relationship between childhood SES and IL-6 seems to be moderated by recent life events, such that individuals with a relatively low childhood SES exhibit an inflammatory phenotype in the context of a high number of recent negative life events.

Daily social interactions, close relationships, and systemic inflammation in two samples: Healthy middle-aged and older adults.

OBJECTIVE Systemic inflammation is thought to be a biological mediator between social relationship quality and premature mortality. Empirical work has yielded mixed support for an association of social relationship variables with systemic inflammation, perhaps due to methodological limitations. To date, research in this literature has focused on global perceptions of social relationships, with limited attention to the covariance of characteristics of daily social interactions with inflammation. Here, we examine whether daily interactions, as assessed by ecological momentary assessment (EMA), associate with peripheral markers of inflammation among midlife and older adults. METHODS Global social support and integration were measured using the Interpersonal Support Evaluation List (ISEL) and the Social Network Index (SNI), respectively, in older adults from the Pittsburgh Healthy Heart Project (PHHP), and in middle-aged adults from the Adult Health and Behavior Project-II (AHAB-II). Using time-sampled EMA, we assessed the proportion of the day spent in positive and negative social interactions. Systemic markers of inflammation were interleukin (IL)-6 and C-reactive protein (CRP). RESULTS Global measures of support and integration did not associate with inflammation in either sample. In older adults, relative frequency of total positive interactions, those with close others (i.e. spouse, friends, family), and those with coworkers predicted lower concentrations of IL-6 in fully adjusted models, accounting for age, sex, race, education, BMI, smoking and alcohol. In middle-aged adults, relative frequency of positive interactions with close others was also inversely associated with IL-6 level and relative frequency of negative marital interactions was unexpectedly inversely associated with CRP level. CONCLUSIONS Characteristics of daily social interactions among midlife and older adults associate with markers of systemic inflammation that are known to predict risk for cardiovascular disease. Ambulatory measures may better capture health-relevant social processes in daily life than retrospective, global self-report measures.

Ethnically-Based Theme House Residency and Expected Discrimination Predict Downstream Markers of Inflammation Among College Students

We examined participation in an ethnically based residential program or “theme house” during the first year of college as a predictor of downstream immune system inflammation among undergraduates. Using a 4-year prospective design, we compared markers of inflammation among Latino/Latina students in a residential theme program with a matched sample of nonresidents. Students provided oral mucosal transudate samples for the assessment of circulating Interleukin 6 (IL-6), an inflammatory cytokine linked to health vulnerabilities. Findings suggest a protective benefit of theme house residency especially among students with anxious expectations of discrimination. Such expectations predicted higher levels of IL-6 after the first year of college among nonresidents only. In years 2–3, following exit from the theme house, the relationship between expected discrimination and IL-6 levels remained positive among nonresidents and was attenuated among residents, controlling for past IL-6 levels. Culturally based spaces may therefore offset the physiological burden of expected discrimination among undergraduates.

Early Life Family Conflict, Social Interactions, and Carotid Artery Intima-Media Thickness in Adulthood.

Objective Conflict in early life family environments is known to affect psychosocial functioning and coping styles into adulthood and is reported to negatively affect access to psychosocial resources that are critical to the management of stress. However, it remains unknown whether early life family conflict similarly affects subclinical cardiovascular disease (CVD) in adulthood. We predicted that family conflict in early life would be associated with greater mean intima-media thickness (IMT), a subclinical marker of CVD risk, in adulthood. Methods Data were collected in a community sample of 503 adults (47.4 % male, mean [standard deviation] age = 42.8 [7.3] years). Associations between family conflict in early life with IMT (assessed using B-mode ultrasound) in adulthood were examined using regression analysis. We also tested for indirect effects of early life family conflict on mean IMT through ecological momentary assessment reports of social interactions, diversity of social roles, and perceived social support. Results Linear regression analyses adjusted for demographics and physiological risk factors showed conflict in early life associated with greater mean IMT (&bgr; = 0.08, t(447) = 2.13, p = .034, R2 = 0.46). Early life conflict was significantly related to diversity of social roles, perceived social support, and ecological momentary assessment reports of pleasant and social conflict interactions. Significant indirect effects of early life conflict on mean IMT were observed through fewer pleasant social interactions and more frequent social conflict interactions in adulthood (&bgr; = 0.001 [95% confidence interval = 0.0001–0.0014] and &bgr; = 0.001 [95% confidence interval = 0.0002–0.0015], respectively). Conclusions These findings provide initial evidence that family conflict in early life heightens CVD risk in adulthood, in part by shaping the quality of adulthood social interactions.