The Systemic Response to Topical Aldara Treatment is Mediated Through Direct TLR7 Stimulation as Imiquimod Enters the Circulation

Abstract Topical application of Aldara cream, containing the Toll-like receptor 7/8 agonist Imiquimod, is a widely used mouse model for investigating the pathogenesis of psoriasis. We have previously used this model to study the effects of peripheral inflammation on the brain, and reported a brain-s...

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Autores principales:	Louis Nerurkar, Alison McColl, Gerard Graham, Jonathan Cavanagh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ee0e4bef1594738b6d440d38972e7be
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spelling	oai:doaj.org-article:2ee0e4bef1594738b6d440d38972e7be2021-12-02T15:04:55ZThe Systemic Response to Topical Aldara Treatment is Mediated Through Direct TLR7 Stimulation as Imiquimod Enters the Circulation10.1038/s41598-017-16707-52045-2322https://doaj.org/article/2ee0e4bef1594738b6d440d38972e7be2017-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16707-5https://doaj.org/toc/2045-2322Abstract Topical application of Aldara cream, containing the Toll-like receptor 7/8 agonist Imiquimod, is a widely used mouse model for investigating the pathogenesis of psoriasis. We have previously used this model to study the effects of peripheral inflammation on the brain, and reported a brain-specific response characterised by increased transcription, infiltration of immune cells and anhedonic-like behavior. Here, we perform a more robust characterisation of the systemic response to Aldara application and find a potent but transient response in the periphery, followed by a prolonged response in the brain. Mass spectrometry analysis of plasma and brain samples identified significant levels of Imiquimod in both compartments at molar concentrations likely to evoke a biological response. Indeed, the association of Imiquimod with the brain correlated with increased Iba1 and GFAP staining, indicative of microglia and astrocyte reactivity. These results highlight the potency of this model and raise the question of how useful it is for interpreting the systemic response in psoriasis-like skin inflammation. In addition, the potential impact on the brain should be considered with regards to human use and may explain why fatigue, headaches and nervousness have been reported as side effects following prolonged Aldara use.Louis NerurkarAlison McCollGerard GrahamJonathan CavanaghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Louis Nerurkar Alison McColl Gerard Graham Jonathan Cavanagh The Systemic Response to Topical Aldara Treatment is Mediated Through Direct TLR7 Stimulation as Imiquimod Enters the Circulation
description	Abstract Topical application of Aldara cream, containing the Toll-like receptor 7/8 agonist Imiquimod, is a widely used mouse model for investigating the pathogenesis of psoriasis. We have previously used this model to study the effects of peripheral inflammation on the brain, and reported a brain-specific response characterised by increased transcription, infiltration of immune cells and anhedonic-like behavior. Here, we perform a more robust characterisation of the systemic response to Aldara application and find a potent but transient response in the periphery, followed by a prolonged response in the brain. Mass spectrometry analysis of plasma and brain samples identified significant levels of Imiquimod in both compartments at molar concentrations likely to evoke a biological response. Indeed, the association of Imiquimod with the brain correlated with increased Iba1 and GFAP staining, indicative of microglia and astrocyte reactivity. These results highlight the potency of this model and raise the question of how useful it is for interpreting the systemic response in psoriasis-like skin inflammation. In addition, the potential impact on the brain should be considered with regards to human use and may explain why fatigue, headaches and nervousness have been reported as side effects following prolonged Aldara use.
format	article
author	Louis Nerurkar Alison McColl Gerard Graham Jonathan Cavanagh
author_facet	Louis Nerurkar Alison McColl Gerard Graham Jonathan Cavanagh
author_sort	Louis Nerurkar
title	The Systemic Response to Topical Aldara Treatment is Mediated Through Direct TLR7 Stimulation as Imiquimod Enters the Circulation
title_short	The Systemic Response to Topical Aldara Treatment is Mediated Through Direct TLR7 Stimulation as Imiquimod Enters the Circulation
title_full	The Systemic Response to Topical Aldara Treatment is Mediated Through Direct TLR7 Stimulation as Imiquimod Enters the Circulation
title_fullStr	The Systemic Response to Topical Aldara Treatment is Mediated Through Direct TLR7 Stimulation as Imiquimod Enters the Circulation
title_full_unstemmed	The Systemic Response to Topical Aldara Treatment is Mediated Through Direct TLR7 Stimulation as Imiquimod Enters the Circulation
title_sort	systemic response to topical aldara treatment is mediated through direct tlr7 stimulation as imiquimod enters the circulation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2ee0e4bef1594738b6d440d38972e7be
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The Systemic Response to Topical Aldara Treatment is Mediated Through Direct TLR7 Stimulation as Imiquimod Enters the Circulation

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