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

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.

• Authors: Takashi Hashimoto, Kent Sakai, Kristen M Sanders, Gil Yosipovitch, Tasuku Akiyama
• Journal: Acta dermato-venereologica (Acta Derm Venereol) Vol. 99 Issue 3 Pg. 298-303 (Mar 01 2019) ISSN: 1651-2057 [Electronic] Sweden
• PMID: 30460374 (Publication Type: Journal Article)

Chemical References

• Antipruritics
• Interleukin-23
• Interleukins
• Janus Kinase Inhibitors
• Piperidines
• Pyrimidines
• Pyrroles
• tofacitinib
• Imiquimod

Topics

• Animals
• Antipruritics (pharmacology)
• Behavior, Animal (drug effects)
• Disease Models, Animal
• Imiquimod
• Interleukin-23 (genetics, metabolism)
• Interleukins (genetics, metabolism)
• Janus Kinase Inhibitors (pharmacology)
• Male
• Mice, Inbred C57BL
• Nerve Fibers (drug effects, metabolism)
• Piperidines (pharmacology)
• Pruritus (chemically induced, enzymology, prevention & control, psychology)
• Psoriasis (chemically induced, drug therapy, enzymology, psychology)
• Pyrimidines (pharmacology)
• Pyrroles (pharmacology)
• Skin (drug effects, enzymology, innervation)
• Interleukin-22