17β-Estradiol enhances expression of inflammatory cytokines and inducible nitric oxide synthase in mouse contact hypersensitivity

The effects of 17β-estradiol (E2) on the expression of cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 in mouse contact hypersensitivity (CHS) were examined. Three week old female mice were ovariectomized, administered 3.2 µg of E2 subcutaneously, the mice sensitized by application of 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (OXA) on their backs, and CHS induced by applying OXA to the auricles. E2 significantly increased mRNA expression of interferon (IFN)-γ and interleukin (IL)-10 in the auricle at 6 and 24 h after allergy elicitation in the ear, respectively, when compared to untreated controls. Although there was no effect of E2 on the expression of IL-4 and COX-2 at any time, the expression of iNOS mRNA was increased by E2 treatment at 48 h after elicitation. E2 also enhanced the expression of tumor necrosis factor (TNF)-α and IL-1β. Histological evaluation revealed that E2 promoted edema of the auricle dermis. The hyperplasia of the epidermis was suppressed by E2 and the cell infiltration observed after elicitation was not altered by E2. These results suggest that E2 enhances the expression of IFN-γ, TNF-α, and IL-1β to augment the edema of auricle dermis in mouse CHS.