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Social regulation of leukocyte homeostasis: the role of glucocorticoid sensitivity - PubMed

Social regulation of leukocyte homeostasis: the role of glucocorticoid sensitivity

Steve W Cole. Brain Behav Immun. 2008 Oct.

Abstract

Recent small-scale genomics analyses suggest that physiologic regulation of pro-inflammatory gene expression by endogenous glucocorticoids may be compromised in individuals who experience chronic social isolation. The present study assessed the relationship between leukocyte distributional sensitivity to glucocorticoid regulation and subjective social isolation in a large population-based sample of older adults. Initial analyses confirmed that circulating neutrophil percentages were elevated, and circulating lymphocyte and monocyte percentages were suppressed, in direct proportion to circulating cortisol levels. However, leukocyte distributional sensitivity to endogenous glucocorticoids was abrogated in individuals reporting either occasional or frequent experiences of subjective social isolation. This finding held in both non-parametric univariate analyses and in multivariate linear models controlling for a variety of biological, social, behavioral, and psychological confounders. The present results suggest that social factors may alter immune cell sensitivity to physiologic regulation by the hypothalamic-pituitary-adrenal axis in ways that could ultimately contribute to the increased physical health risks associated with social isolation.

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Figures

FIGURE 1
FIGURE 1. Sensitivity of circulating leukocyte subset distributions to cortisol level

Regression lines indicate the variation in hematologic paramters as a function of cortisol level in 812 non-lonely participants (solid line) and 183 lonely participants (dashed line) for (a.) percent lymphocytes, (b.) percent monocytes, (c.) percent neutrophils, and (d.) neutrophil / monocyte ratios. p-values give statistical significance of the slope of regression lines for non-lonely individuals, lonely individuals, and the difference between groups (Cortisol × Loneliness interaction) in analyses controlling for BMI, Age, Sex, Age × Sex interaction, smoking, alcohol consumption, SES, physical health status, depression, and objective social isolation.

FIGURE 2
FIGURE 2. Relationship between subjective social isolation and magnitude of leukocyte distributional sensitivity to cortisol level

Data represent mean ± standard error of sensitivity coefficients relating variation in cortisol concentration to (a.) neutrophil / lymphocyte ratios, and (b.) neutrophil / monocyte ratios at varying levels of loneliness. p-values denote statistical significance of profile contrasts comparing adjacent sensitivity coefficients.

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