Janus kinase inhibitor delgocitinib suppresses pruritus and nerve elongation in an atopic dermatitis murine model

Atopic dermatitis (AD) is a chronic inflammatory skin disease with intense pruritus [ [1] Weidinger S. Beck L.A. Bieber T. Kabashima K. Irvine A.D. Atopic dermatitis. Nat. Rev. Dis. Primers. 2018; 4: 1 Crossref PubMed Scopus (275) Google Scholar ]. It has been reported that T helper type 2 (Th2) cytokines play essential roles in the pathogenesis of AD [ [1] Weidinger S. Beck L.A. Bieber T. Kabashima K. Irvine A.D. Atopic dermatitis. Nat. Rev. Dis. Primers. 2018; 4: 1 Crossref PubMed Scopus (275) Google Scholar ]. In fact, anti-interleukin (IL)-4 receptor subunit alpha antibody dupilumab, which blocks the IL-4 and IL-13 signal, was effective for treating both dermatitis and pruritus in AD patients [ [2] Simpson E.L. Bieber T. Guttman-Yassky E. Beck L.A. Blauvelt A. Cork M.J. Silverberg J.I. Deleuran M. Kataoka Y. Lacour J.P. Kingo K. Worm M. Poulin Y. Wollenberg A. Soo Y. Graham N.M. Pirozzi G. Akinlade B. Staudinger H. Mastey V. Eckert L. Gadkari A. Stahl N. Yancopoulos G.D. Ardeleanu M. Solo S. Investigators, two phase 3 Trials of Dupilumab versus placebo in atopic dermatitis. N. Engl. J. Med. 2016; 375: 2335-2348 Crossref PubMed Scopus (1108) Google Scholar ]. Recently, the antibody targeting IL-31, another Th2 cytokine inducing pruritus, has been reported to suppress pruritus and dermatitis of AD [ [3] Ruzicka T. Hanifin J.M. Furue M. Pulka G. Mlynarczyk I. Wollenberg A. Galus R. Etoh T. Mihara R. Yoshida H. Stewart J. Kabashima K. Group X.S. Anti-interleukin-31 receptor a antibody for atopic dermatitis. N. Engl. J. Med. 2017; 376: 826-835 Crossref PubMed Scopus (364) Google Scholar ]. These clinical findings suggested that the strategy targeting the Th2 cytokines such as IL-4, IL-13 and IL-31 is effective in AD.