Chronic psychological stress aggravates psoriasis-like skin inflammation via overactivation of ₂-adrenoceptor and nuclear factor kappa B pathways

The relationship between psoriasis severity and psychological stress has been described in several studies. However, the mechanism by which chronic stress exacerbates psoriasis is not completely understood. This study aimed at investigating whether chronic psychological stress can aggravate psoriasis-like skin inflammation. Mice were subjected to a restraint stress model and topically treated with imiquimod (IMQ). Differentiated human keratinocytes were treated with high epinephrine levels and IMQ in vitro. Stress aggravated macroscopic features and the increase in epidermal thickness induced by IMQ in mouse skin. The increase in NF-kappa B and IL-17A expression induced by IMQ was potentiated by chronic stress in mouse skin. The skin of stressed mice treated with IMQ showed higher levels of beta(2)-adrenergic receptors (beta(2)-AR). In human keratinocytes, high epinephrine levels exacerbated the increase in the levels of beta(2)-AR and IL-17A induced by IMQ. beta-AR antagonist reversed the effects of chronic stress in IMQ-induced inflammation both in vivo and in vitro. In conclusion, stress-stimulated overactivation of the beta(2)-AR and NF-kappa B pathways potentiates a Th1/Th17 profile leading to an exacerbation of psoriasis.