A murine model of epicutaneous protein sensitization is useful to study efficacies of topical drugs in atopic dermatitis

• Published in: International immunopharmacology Vol. 10; no. 4; pp. 377 - 384
• Main Authors: Lehto, Maili, Savinko, Terhi, Wolff, Henrik, Kvist, Peter H, Kemp, Kaare, Lauerma, Antti, Alenius, Harri
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01-04-2010; Elsevier
• Subjects: Administration, Topical; Allergic diseases; Animal models; Animals; Anti-Allergic Agents - administration & dosage; Anti-Allergic Agents - therapeutic use; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - therapeutic use; Atopic dermatitis; Betamethasone Valerate - administration & dosage; Betamethasone Valerate - therapeutic use; Biological and medical sciences; Calcineurin inhibitor; Calcineurin Inhibitors; Corticosteroid; Cytokines; Cytokines - biosynthesis; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - pathology; Disease Models, Animal; Enterotoxins - immunology; Female; Immunoglobulin A - immunology; Immunoglobulin E - immunology; Immunohistochemistry; Immunopathology; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - therapeutic use; Medical sciences; Mice; Mice, Inbred BALB C; Mouse model; Ovalbumin - immunology; Pharmacology. Drug treatments; Phosphodiesterase 4; Phosphodiesterase Inhibitors - administration & dosage; Phosphodiesterase Inhibitors - therapeutic use; Proteins - administration & dosage; Proteins - immunology; Reverse Transcriptase Polymerase Chain Reaction; Skin - pathology; Skin allergic diseases. Stinging insect allergies; Tacrolimus - administration & dosage; Tacrolimus - therapeutic use; Xanthines - administration & dosage; Xanthines - therapeutic use; Phosphodiesterase 4; Corticosteroid; Mouse model; Calcineurin inhibitor; Cytokines; Atopic dermatitis; Allergy; Animal model; Skin disease; Esterases; Phosphoric diester hydrolases; Atopy; Local administration; Sensitization; Drug; Immunopathology; 3',5'-Cyclic-nucleotide phosphodiesterase; Enzyme; Treatment efficiency; Rodentia; Cytokine; Protein; Vertebrata; Mammalia; Mouse; Hydrolases; Topical administration
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2010.01.001

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-γ 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.