THE EFFECT OF CHRONIC PSYCHOLOGICAL STRESS ON THE CUTANEOUS IMMUNE RESPONSE IN CONTACT HYPERSENSITIVITY REACTIONS

Purpose: Our objective is to determine the role of chronic psychological stress on the cutaneous immune response during contact hypersensitivity (CHS) reactions. We hypothesize that chronic psychological stress induces suppression of the cutaneous immune response mediated by a disruption of leukocyte trafficking. Methods: Restraint stress was applied to female BALB/c mice for 2 hours for 30 days. The sensitizing agent, oxazalone, was then applied on the abdomen, and the mice were then challenged on the ear 7 days later. Weight measurements and corticosterone levels were evaluated. Ear swelling was measured by caliper and histology to assess inflammation. In vitro and in vivo assays were performed to analyze leukocyte proliferation. Cytokine and chemokine ELISAs were performed on the lymph node culture supernatant and ear homogenate. Flow cytometry was performed on draining lymph nodes. Circulating leukocytes were analyzed by Hemavet before and after the stressing period. Results: Decreased weight gain and elevated serum corticosterone in the Stressed group confirmed differential stress levels. Ear swelling in response to oxazalone challenge was reduced in the Stressed group. In vitro and in vivo analysis showed no difference in T cell proliferation or overall cell proliferation in auricular lymph nodes, respectively. Common inflammatory cytokine and chemokine concentration in ear homogenates at the site of inflammation did not significantly differ between the two groups. Flow cytometric analysis of auricular draining lymph nodes showed no difference in T cell activation, however CD4+ and CD8+ T cell percentages were elevated in auricular lymph nodes of the Stressed group. Hemavet analysis showed a reduction in circulating neutrophils, lymphocytes, and monocytes in the Stressed group in addition to overall reduced white blood cell number. Conclusions: Our results show that chronic restraint stress suppresses the cutaneous immune response in CHS reactions. The mechanism of this suppression is not due to reduced T cell proliferation, T cell activation, or total cell proliferation in draining lymph nodes. Our results indicate reduced lymphocyte, neutrophil, and monocyte trafficking to the site of inflammation and an accumulation of CD4+ and CD8+ T cells in draining lymph nodes may contribute to the suppression. Future studies will be performed to analyze CD4+ T cell, CD8+ T cell, neutrophil, and macrophage population at the site of inflammation using immunofluorescence staining.