576 Difamilast, a new topical PDE4 inhibitor, ameliorates not only chronic allergic dermatitis but also idiopathic dermatitis induced by psychological stress in mice

Difamilast is a novel PDE4 inhibitor with the strongest inhibitory activity against PDE4B among four subtypes. Moizerto® ointment (0.3%, 1% difamilast) has been recently approved for treatment of atopic dermatitis (AD) in Japan. Exogenous antigen stimulation or psychological stress can trigger exacerbate AD symptoms. In this study, we evaluated therapeutic effects difamilast, tacrolimus, and betamethasone valerate on two different mice models dermatitis: one was chronic contact hypersensitivity (CCH) induced by repeated application hapten every 2 days 52 days, other idiopathic due to persistent self-scratching three times week 16 weeks, followed individual housing (social isolation) 6 months. Efficacy assessed topical each drug 4 weeks after established. CCH model, difamilast group significantly improved skin hyperplasia from 0.03% 3% dose-responsibly inhibition inflammatory cell infiltration such as T cells, eosinophils, neutrophils. Betamethasone (0.12%) more strongly than ointment. Tacrolimus (0.1%) temporarily symptoms, but eventually had no effect. (1%, 3%) symptoms decrease MIP-1 alpha MIP-2 content. slightly while exacerbated it. Notably, ameliorates both stress-induced dermatitis. worsened probably atrophy steroid’s side effect tacrolimus weak models. Therefore, expected be possible allergic stress-exacerbated