Stress-Mediated Physiological Epinephrine Levels Reduce Imiquimod-Induced Psoriasis-Like Skin Inflammation

Psychological stress-mediated systemic hormones can aggravate psoriasis severity. However, some studies have shown that stress can also ameliorate this disease. We aimed to investigate the effects of a high physiological epinephrine dose, as observed in stressed individuals, in imiquimod (IMQ)-induced skin inflammation ex vivo. Normal human skin explants were treated ex vivo with 56 nM (a high physiological level) epinephrine, and then three days later, topically treated with IMQ for 6 consecutive days. Human keratinocytes were treated in vitro with IMQ or epinephrine. The administration of 56 nM epinephrine reduced the epidermal area and increased the protein levels of IL-10 in IMQ-treated human skin. The blockade of β1- andβ2-adrenergic receptors (β1-/β2-AR), the IL-10 receptor, and cAMP reversed the reduction in epidermal area induced by epinephrine levels (56 nM) in IMQ-treated skin. In human keratinocytes, a physiological epinephrine level and IMQ increased the protein levels of β2-AR, cAMP, and IL-10. In conclusion, a high physiological level of epinephrine ameliorates IMQ-induced skin inflammation via cAMP and IL-10 production.