Anti‐inflammatory effect of lanoconazole on 12‐O‐tetradecanoylphorbol‐13‐acetate– and 2,4,6‐trinitrophenyl chloride–induced skin inflammation in mice
Aki Nakamura  Hideya Uratsuji  Yoshihito Yamada  Kei Hashimoto  Naoki Nozawa  Tatsumi Matsumoto
First published: 14 November 2019 https://doi.org/10.1111/myc.13034
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/myc.13034
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Abstract
Background
Lanoconazole (LCZ) is a topical antifungal agent clinically used to treat fungal infections such as tinea pedis. LCZ has not only antifungal effects but also anti‐inflammatory effects, which have the potential to provide additional clinical benefits. However, the characteristic features of the inhibitory effects of LCZ on skin inflammation remain unclear.

Objective
We evaluated the inhibitory effects of topical application of LCZ, and compared the effects of LCZ with those of other antifungal agents including liranaftate, terbinafine, and amorolfine.

Methods
Each antifungal agent was topically applied on 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced irritant dermatitis and 2,4,6‐trinitrophenyl chloride‐induced contact dermatitis in mice (BALB/c). The ear thickness, myeloperoxidase activity and inflammatory mediator contents were evaluated.

Results
LCZ dose‐dependently suppressed 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced irritant dermatitis, suppressed the production of neutrophil chemotactic factors such as keratinocyte‐derived chemokine and macrophage inflammatory protein‐2, and inhibited neutrophil infiltration to the inflammation site. Moreover, 1% LCZ reduced the ear swelling in mice with 2,4,6‐trinitrophenyl chloride‐induced contact dermatitis in accordance with the inhibition of interferon‐γ production. The inhibitory potency of LCZ on these types of dermatitis in mice was stronger than that of other types of antifungal agents.

Conclusion
The anti‐inflammatory effects of LCZ were exerted through the inhibition of inflammatory mediator production. These effects may contribute to the relief of dermatitis symptoms in patients with tinea pedis.