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Antipruritic Effects of Janus Kinase Inhibitor Tofacitinib in a Mouse Model of Psoriasis
- Source :
- Acta Dermato-Venereologica, Vol 99, Iss 3, Pp 298-303 (2019)
- Publication Year :
- 2019
- Publisher :
- Medical Journals Sweden AB, 2019.
-
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.
- Subjects :
- Male
0301 basic medicine
IL-31
Imiquimod
Dermatology
Pharmacology
Interleukin-23
030207 dermatology & venereal diseases
03 medical and health sciences
Nerve Fibers
0302 clinical medicine
Piperidines
Psoriasis
lcsh:Dermatology
medicine
Interleukin 23
Animals
Janus Kinase Inhibitors
Pyrroles
Antipruritic
Skin
Janus kinase inhibitor
Tofacitinib
Behavior, Animal
Janus kinase 1
business.industry
Interleukins
Pruritus
Antipruritic Effect
AK inhibitor
Antipruritics
General Medicine
lcsh:RL1-803
medicine.disease
Mice, Inbred C57BL
chronic itch
Disease Models, Animal
Pyrimidines
030104 developmental biology
scratching
business
medicine.drug
Subjects
Details
- ISSN :
- 00015555
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Acta Dermato Venereologica
- Accession number :
- edsair.doi.dedup.....a0b4205c3a509c9bfbaac466e1fe51d9