Anti-inflammatory effect of lanoconazole on 12-O-tetradecanoylphorbol-13-acetate- and 2,4,6-trinitrophenyl chloride-induced skin inflammation in mice

Mycoses. 2020 Feb;63(2):189-196. doi: 10.1111/myc.13034. Epub 2019 Nov 27.

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.

Keywords: CXC; anti-inflammatory agents; antifungal agents; chemokines; dermatitis:contact; dermatitis:irritant; dermatomycoses; lanoconazole; pharmacology.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antifungal Agents / therapeutic use
  • Dermatitis, Contact / drug therapy*
  • Dermatitis, Contact / etiology
  • Dermatitis, Contact / prevention & control
  • Dose-Response Relationship, Drug
  • Ear, External / drug effects
  • Ear, External / pathology
  • Female
  • Imidazoles / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Picrates / adverse effects*
  • Tetradecanoylphorbol Acetate / adverse effects*
  • Tinea Pedis / complications
  • Tinea Pedis / pathology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antifungal Agents
  • Imidazoles
  • Picrates
  • latoconazole
  • picric acid
  • Tetradecanoylphorbol Acetate