Methodological refinement of Aldara-induced psoriasiform dermatitis model in mice

Szabina Horváth,Anikó Perkecz,Rita Komlódi,Erika Pintér,Rolland Gyulai,Ágnes Kemény

doi:10.1038/s41598-019-39903-x

Szabina Horváth, Anikó Perkecz + Show 4 more

Open Access

https://doi.org/10.1038/s41598-019-39903-x

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Journal: Scientific Reports	Publication Date: Mar 6, 2019
Citations: 32	License type: open-access

Affiliation: University of Pecs

Abstract

Imiquimod (IMQ)-induced skin inflammation is currently the most widely accepted psoriasis animal model, however, it features several limitations. We have modified the IMQ-model to minimize its systemic effects towards effectively maintaining the characteristic skin reactions. The original protocol (OP) uses 62.5 mg Aldara cream (or vaseline) on the shaved back skin of mice for 4 days. In contrast, in our modified protocol (MP) 25 mg Aldara and vaseline are applied simultaneously in separate Finn chambers over the dorsal skin of mice. In both the OP and MP groups, histology showed unequivocal hallmarks of psoriasiform dermatitis. Additionally, skin scaling and blood perfusion values were similar. While Aldara elicited significantly increased skin thickness in the MP group, significant weight loss, spleen enlargement, increased inflammatory cytokine levels in plasma, and treatment related death were only observed in the OP group. Our new method reproduces psoriatic skin alterations highlighting considerably reduced systemic inflammatory reactions. Possessing psoriasiform and control skin areas on the same mouse also reduces inter-individual differences. Additionally, the new method permits prolonged IMQ treatment studies to mimic the chronic nature of psoriasis. Finally, our experimental approach may also be used in other mouse models, to prevent the undesired systemic effects of topically applied drugs.

Highlights

Aldara (5% imiquimod)-induced acute skin inflammation became the most widely used animal model of psoriasis since it was first published in 20091
Erythema developed following the second treatment using Aldara, and soon thereafter, scaling appeared on the third day which continually increased in severity up to the end of the experiment in both original protocol (OP) and modified protocol (MP) group (Fig. 1a)
Aldara treatment induced elevated microcirculation in the dorsal skin compared to the vaseline-treated sites, represented by the red areas on the color pictures assessed by Laser Speckle Contrast Analysis (LASCA) laser Speckle instrument (Fig. 1b)

Summary

Introduction

Aldara (5% imiquimod)-induced acute skin inflammation became the most widely used animal model of psoriasis since it was first published in 20091. The overuse of the Aldara cream and its ingestion is the most problematic since it can cause severe systemic inflammation indicated by splenomegaly, worsened general condition and untimely death of the animals[8]. This can contribute to the phenotypic variability observed in this model and it may likely be the reason for the different treatment regimens applied by various authors[1,9,10].

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