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

Takashi Hashimoto, Kent Sakai, Kristen M. Sanders, Gil Yosipovitch, Tasuku Akiyama

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)298-303
Number of pages6
JournalActa dermato-venereologica
Volume99
Issue number3
DOIs
StatePublished - Mar 1 2019

Fingerprint

Antipruritics
imiquimod
Janus Kinases
Nerve Fibers
Psoriasis
Cytokines
Janus Kinase 3
Janus Kinase 1
Skin
tofacitinib
Messenger RNA

Keywords

  • chronic itch
  • IL-31
  • psoriasis
  • scratching
  • AK inhibitor

ASJC Scopus subject areas

  • Dermatology

Cite this

Antipruritic Effects of Janus Kinase Inhibitor Tofacitinib in a Mouse Model of Psoriasis. / Hashimoto, Takashi; Sakai, Kent; Sanders, Kristen M.; Yosipovitch, Gil; Akiyama, Tasuku.

In: Acta dermato-venereologica, Vol. 99, No. 3, 01.03.2019, p. 298-303.

Research output: Contribution to journalArticle

Hashimoto, Takashi ; Sakai, Kent ; Sanders, Kristen M. ; Yosipovitch, Gil ; Akiyama, Tasuku. / Antipruritic Effects of Janus Kinase Inhibitor Tofacitinib in a Mouse Model of Psoriasis. In: Acta dermato-venereologica. 2019 ; Vol. 99, No. 3. pp. 298-303.
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