Abstract # 1815 Stress and the cholinergic system: the cholinergic pathway in allergic inflammation aggravated by psychosocial stress exposure is not anti-inflammatory

Abstract

An anti-inflammatory role for acetylcholine in chronic inflammation has extensively been studied. In fact it’s beneficial effects were shown in many inflammatory diseases driven by TNF α , most prominently sepsis. Lately it was suggested to also play a role in inflammatory diseases aggravated by stress. One cardinal inflammatory disease with high sensitivity to stress is atopic dermatitis, which is a non-communicable disease modeled in mice by subcutaneous allergic sensitization and intradermal provocation with allergen. Exposing such mice to 24 h of noise stress worsens neuropeptide driven disease severity. Here, we investigated the effect of stress-exposure on Chrna7 driven TNF α expression in this model. We found significantly upregulated expression of Chrna7 and it’s ligands acetylcholine and SLURP-1 in response to stress both by qRTPCR of full thickness skin samples and by immunohistomorphometry of mast cells in skin of mice with allergic dermatitis while TNF α and IL1 β levels decreased and IL10 and TGF β levels increased. This was associated with a denser cutaneous infiltrate and increased epidermal thickness. Treatment of mice with NGF neutralizing antibodies reversed the stress effects. Translating these findings to the human level, we found that serum samples of patients with atopic dermatitis contained higher levels of SLURP1 when stressed. We therefor conclude that in allergic dermatitis, cholinergic regulation in response to stress participates in inflammatory circuits worsening the disease.