Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami, 1600 NW 10th Ave RMSB2063, Miami, FL 33136, USA.
Acta Derm Venereol. 2019 Mar 1;99(3):298-303. doi: 10.2340/00015555-3086.
The Janus kinase 1/3 inhibitor tofacitinib has demonstrated an antipruritic effect in two phase III studies in psoriasis. However, the mechanisms behind this antipruritic effect are still unknown. We presently investigated whether tofacitinib affects spontaneous itch as well as expression of itch-related cytokines and epidermal nerve fiber density (ENFD) in the imiquimod-induced mouse model of psoriasis. Psoriasis-like skin lesions were produced by daily topical application of imiquimod to the back skin. Imiquimod treatment resulted in spontaneous scratching, which was significantly inhibited by tofacitinib treatment. Imiquimod treatment significantly increased mRNA expression of Il22, Il23, and Il31, reduced peptidergic ENFD, and increased nonpeptidergic ENFD compared to naive mice. Tofacitinib significantly decreased the expression of those cytokines and increased peptidergic ENFD without a significant effect on nonpeptidergic ENFD. Tofacitinib may inhibit psoriatic itch through inhibition of cytokine expression as well as modulation of epidermal innervation.
Janus 激酶 1/3 抑制剂托法替尼在两项银屑病的 III 期研究中表现出止痒作用。然而，这种止痒作用的机制尚不清楚。我们目前研究了托法替尼是否会影响咪喹莫特诱导的银屑病样小鼠模型中的自发性瘙痒以及与瘙痒相关的细胞因子和表皮神经纤维密度（ENFD）的表达。通过每天在背部皮肤涂抹咪喹莫特来产生银屑病样皮肤损伤。咪喹莫特处理导致自发性搔抓，托法替尼处理显著抑制了搔抓。与正常小鼠相比，咪喹莫特处理显著增加了 Il22、Il23 和 Il31 的 mRNA 表达，减少了肽能 ENFD，增加了非肽能 ENFD。托法替尼显著降低了这些细胞因子的表达，增加了肽能 ENFD，而对非肽能 ENFD 没有显著影响。托法替尼可能通过抑制细胞因子表达以及调节表皮神经支配来抑制银屑病瘙痒。
