Document Type

Article

Publication Date

2018

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

Abstract

Urbanization is on the rise, although the urban environment is linked to an increased prevalence of both physical and mental disorders. Human and animal studies suggest that an over-reactive immune system not only accompanies stress-associated disorders, but might even be causally involved in their pathogenesis. Here we show in young (mean age, years, (SD): rural, 25.1 (0.78); urban, 24.5 (0.88)) healthy human volunteers that urban upbringing in the absence of pets (n=20), relative to rural upbringing in the presence of farm animals (n=20), was associated with an exaggerated systemic immune activation following psychosocial stress. Questionnaires, plasma cortisol, and salivary alpha-amylase, however, indicated that the experimental protocol was more stressful and anxiogenic for rural participants. In detail, in response to the Trier Social Stress Test (TSST), participants with an urban versus rural upbringing showed a more pronounced increase in the number of peripheral blood mononuclear cells (PBMCs) and plasma interleukin (IL)-6 concentrations. Moreover, ex vivo cultured PBMCs from urban versus rural participants secreted more IL-6 in response to the T cell-specific mitogen concanavalin A (ConA). In turn, anti-inflammatory IL-10 secretion was suppressed following TSST in urban versus rural participants, suggesting immunoregulatory deficits in urban participants following social stress. Together, our findings support the hypothesis that urban upbringing in the absence of pets, in contrast to rural upbringing in the presence of farm animals, increases the vulnerability for stress-associated physical and mental disorders by compromising adequate resolution of systemic immune activation following social stress and, in turn, aggravating stress-associated systemic immune activation.

Comments

This pre-print was later published in Proceedings of the National Academy of Sciences of the United States of America as "Less immune activation following social stress in rural vs. urban participants raised with regular or no animal contact, respectively."

https://doi.org/10.1073/pnas.1719866115

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