title: A murine model of epicutaneous protein sensitization is useful to study efficacies of topical drugs in atopic dermatitis.
abstract: We studied the suitability of our murine model for the treatment trials of atopic dermatitis (AD). In this model topical application of ovalbumin (OVA) together with bacterial superantigen, staphylococcal enterotoxin B (SEB) induces a cutaneous disease resembling AD. Injured mouse skin was treated with three different drugs: a class III corticosteroid, a calcineurin inhibitor and a type 4 phosphodiesterase inhibitor. One-week treatment with corticosteroid and phosphodiesterase inhibitor remarkably decreased both epidermal and dermal thickness, whereas the calcineurin inhibitor affected only the epidermal thickness. All investigated drugs reduced the infiltration of eosinophils and mast cells onto OVA/SEB sensitized skin areas, whereas CD4+ and CD8+ T cells as well as CD11c+ dendritic cells variously diminished after corticosteroid and calcineurin inhibitor treatments. Cutaneous expression of interleukin -4, -13, -10 and interferon-gamma also decreased differently depending on drug type. Interestingly, the calcineurin inhibitor and phosphodiesterase inhibitor increased total IgE antibodies and decreased SEB-specific IgG2a antibodies in OVA/SEB sensitized mice. All these drugs can ameliorate cutaneous inflammation, although the degree of recovery depends on the type of the drug. In summary, our results show that this mouse model can be used to test new topical treatments for AD.
authors.affiliation: Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, FIN-00250 Helsinki, Finland. maili.lehto@ttl.fi
authors.forename: Maili
authors.initials: M
authors.lastname: Lehto
authors.forename: Terhi
authors.initials: T
authors.lastname: Savinko
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.forename: Peter H
authors.initials: PH
authors.lastname: Kvist
authors.forename: Kaare
authors.initials: K
authors.lastname: Kemp
authors.forename: Antti
authors.initials: A
authors.lastname: Lauerma
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
mesh_terms: D000287:Administration, Topical; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001624:Betamethasone Valerate / Q000008:administration & dosage / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D007070:Immunoglobulin A / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011506:Proteins / Q000008:administration & dosage / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000473:pathology; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use; D014970:Xanthines / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D065095:Calcineurin Inhibitors; D016207:Cytokines; D004768:Enterotoxins; D007070:Immunoglobulin A; D007166:Immunosuppressive Agents; D010726:Phosphodiesterase Inhibitors; D011506:Proteins; D014970:Xanthines; D007073:Immunoglobulin E; C031818:enterotoxin B, staphylococcal; D010047:Ovalbumin; D001624:Betamethasone Valerate; C466758:cipamfylline; D016559:Tacrolimus