title: Topical imiquimod yields systemic effects due to unintended oral uptake.
abstract: Repetitive application of topical imiquimod is used as an experimental model for the induction of psoriasiform skin lesions in mice. The model is characterized by several inflammatory processes, including cytokine production both locally and systemically, cellular infiltration, and splenomegaly. To investigate the production of type I interferons in response to imiquimod-containing Aldara cream, IFNβ-luciferase reporter mice were imaged in vivo and ex vivo. Type I interferons were found to be produced in the skin, but also in the intestinal system caused by unintended ingestion of imiquimod by the mice. Through the use of Elizabethan collars to prevent ingestion, these effects, including psoriasiform lesions were nearly completely prevented. Our findings reveal that topical treatment with Aldara induces a psoriasiform skin inflammation, but that its mode of action depends on ingestion of the chemical, which leads to systemic responses and affects local inflammation. Therefore, potential ingestion of topical treatments during experimental procedures should be taken into account during assessment of cutaneous inflammatory parameters in skin disease models.
authors.affiliation: Inflammation Research Center, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Lynda
authors.initials: L
authors.lastname: Grine
authors.affiliation: Inflammation Research Center, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Steeland
authors.affiliation: Inflammation Research Center, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: Van Ryckeghem
authors.affiliation: Inflammation Research Center, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Marlies
authors.initials: M
authors.lastname: Ballegeer
authors.affiliation: Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.|Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.|Molecular Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lienenklaus
authors.affiliation: Molecular Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Laboratory of Gene Therapy, Faculty of Veterinary Sciences, Ghent University, Ghent, Belgium.
authors.forename: Niek N
authors.initials: NN
authors.lastname: Sanders
authors.affiliation: Inflammation Research Center, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Roosmarijn E
authors.initials: RE
authors.lastname: Vandenbroucke
authors.affiliation: Inflammation Research Center, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Claude
authors.initials: C
authors.lastname: Libert
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects*; D000818:Animals; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D000077271:Imiquimod; D007370:Interferon Type I / Q000096:biosynthesis; D051379:Mice; D010641:Phenotype; D011565:Psoriasis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology
chemical_list: D000634:Aminoquinolines; D007370:Interferon Type I; D000077271:Imiquimod
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