The systemic response to topical Aldara treatment is mediated through direct TLR7 stimulation as Imiquimod enters the circulation

Nerurkar, L., McColl, A., Graham, G. and Cavanagh, J. (2017) The systemic response to topical Aldara treatment is mediated through direct TLR7 stimulation as Imiquimod enters the circulation. Scientific Reports, 7(1), 16570. (doi: 10.1038/s41598-017-16707-5) (PMID:29185473) (PMCID:PMC5707416)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cavanagh, Professor Jonathan and NERURKAR, LOUIS and McColl, Dr Alison and Graham, Professor Gerard
Authors: Nerurkar, L., McColl, A., Graham, G., and Cavanagh, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Scientific Reports 7(1):16570
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
657471Consortium of Neuroimmunology of Mood Disorders and Alzheimer's DiseaseJonathan CavanaghWellcome Trust (WELLCOTR)104025/Z/14/ZIHW - MENTAL HEALTH & WELLBEING