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Itching in a trichophytin contact dermatitis mouse model and the antipruritic effect of antifungal agents
Author(s) -
Nakamura T.,
Yoshida N.,
Anzawa K.,
Nishibu A.,
Mochizuki T.
Publication year - 2019
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/ced.13719
Subject(s) - scratching , ketoconazole , itching , medicine , chemokine , pharmacology , trichophyton , immunology , atopic dermatitis , dermatology , inflammation , antifungal , physics , acoustics
Summary Background Tinea is an infectious disease by dermatophytes, of which Trichophyton species accounts for the overwhelming majority of case. Tinea often causes itching with inflammation. In terms of pruritus by fungal infection, however, tinea has not been investigated sufficiently to date. Aim To evaluate itch caused by Trichophyton infection and the effect of antifungal agents on the infection, by measuring scratch behaviour and profiles of inflammatory cytokines and chemokines. Methods We used a previously established mouse model of contact hypersensitivity induced by trichophytin, a crude extract from Trichophyton mentagrophytes . Scratching behaviour was recorded using a counting device that measured an electric current induced in a coil by movement of magnets that had been inserted into the hind paws of each animal. We investigated expression of various genes in lesional skin of mice and in normal human epidermal keratinocytes. We also investigated the antipruritic effects of the corticosteroid dexamethasone (DEX) and three antifungal agents: ketoconazole (KCZ), terbinafine (TBF) and liranaftate (LNF). Results Biphasic peaks of scratching were observed at 1 h and at 6–7 h during an observation period of 14 h after trichophytin induction. For lesional skin, RNA was extracted 24 h after trichophytin challenge, and increased expression was seen in the genes for interleukin (IL)‐17A, interferon‐γ, tumour necrosis factor (TNF)‐α, macrophage inflammatory protein (MIP)‐2 and Dectin‐1, whereas there was no obvious change in the genes for IL‐31 and prostaglandin (PG)E2. Furthermore, KCZ inhibited histidine decarboxylase (HDC) expression in vitro and in vivo , and inhibited scratching in the very early phase. LNF inhibited expression of thymic stromal lymphopoietin (TSLP) and IL‐8 in vitro , and TSLP, TNF‐α, IL‐1α and MIP2 in vivo , and also scratching in the early phase. TBF did not induce any significant alterations in either gene expression or scratching. DEX suppressed expression of all the chemical mediators except HDC in vitro and in vivo , and inhibited scratching. Conclusion Antifungals can inhibit itching induced by fungal infection through different mechanisms.