The Effect of Chronic Psychological Stress on the Cutaneous Immune Response in the Development of a Contact Hypersensitivity Reaction

Increasing evidence demonstrates that psychological stress can have an impact on the cutaneous immune response. While there have been many studies examining the impact of acute stress on an allergic contact dermatitis model, there are few studies concerning the impact of chronic psychological stress. Furthermore, the mechanism of the impact of chronic stress on contact hypersensitivity remains to be fully explored. Here we show that chronic restraint stress induces activation of the hypothalamus-pituitary-adrenal axis and delays weight gain in female BALB/c mice. In addition, we observed that chronic psychological stress reduces the cutaneous immune response in a contact hypersensitivity reaction. This suppression was not observed 30 days after stress cessation, suggesting the impact of chronic stress is a transient occurrence. Additionally, chronic stress does not influence T cell proliferation, activation, or sensitivity to glucocorticoids. In response to contact hypersensitivity, chronic stress induces a decrease in overall circulating white blood cells, lymphocytes, and monocytes. This correlated to decreased dermal infiltrate and increased percentages of CD4+ and CD8+ T cells in auricular lymph nodes. In addition, decreased amounts of local IFN-γ were observed in inflamed ear tissue of chronically stressed mice. Overall, the results suggest that chronic psychological stress reduces contact hypersensitivity reactions in a relatively transient manner and disrupts local immune cell trafficking resulting in reduced IFN-γ production.