Content » Vol 99, Issue 3

Investigative Report

Antipruritic Effects of Janus Kinase Inhibitor Tofacitinib in a Mouse Model of Psoriasis

Takashi Hashimoto, Kent Sakai, Kristen M. Sanders, Gil Yosipovitch, Tasuku Akiyama
DOI: 10.2340/00015555-3086

Abstract

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.

Significance

Tofacitinib, a drug that inhibits Janus kinases 1 and 3, has been shown to reduce itch in clinical trials of psoriasis. However, the exact mechanism for this anti-itch effect is still unclear. This study investigates the effects of tofacitinib treatment in a mouse model of psoriasis. Tofacitinib reduced scratching in this model. Additionally, tofacitinib rescued the increased mRNA levels of Il22, Il23, and Il31, 3 cytokines that are known to be related to itch. Finally, tofacitinib recovered the reduction in peptidergic nerves in the epidermis of psoriasis model mice. Therefore, tofacitinib could reduce itch through regulation of cytokines and epidermal nerves.

Supplementary content

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