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IL-4/IL-13 antagonist DNA vaccination successfully suppresses Th2 type chronic dermatitis

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Summary Background 

Atopic dermatitis (AD) is a chronic disease with a Th2-type-cytokine dominant profile. Several cytokines and related peptides have been used for the treatment of AD but they were ineffective because of their limited biological half-life. We have recently developed a highly efficient mouse dominant negative interleukin (IL)-4/IL-13 antagonist (IL-4DM), which blocks both IL-4 and IL-13 signal transductions. Objective 

To examine the effects of IL-4DM in vivo in an AD model induced by the repeated exhibition of oxazolone (OX). Methods 

Plasmid DNA was injected intraperitoneally to cause an experimental AD-like dermatitis. The effect was evaluated by ear thickness, histological findings, and mast cells counts in the inflamed skin. The plasma IgE and histamine levels were measured. Cytokine production in skin and splenocytes were also analysed. Results 

Mice treated with control plasmid developed marked dermatitis with mast cells and eosinophil infiltration, and had increased plasma IgE and histamine levels with a Th2 type splenocyte cytokine profile. Treatment with mouse IL-4 DNA augmented the ear swelling and thickness with an increased dermal eosinophil count, plasma histamine level, and production of splenocyte IL-4. However, IL-4DM treatment successfully controlled the dermatitis, decreased the mast cell and eosinophil count, and suppressed plasma IgE and histamine levels. Splenocytes produced an increased level of IFN-γ. Conclusion 

These data showed that the simultaneous suppression of IL-4/IL-13 signals successfully controlled Th2-type chronic dermatitis. IL-4DM DNA treatment is a potent therapy for AD and related diseases.
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Keywords: DNA vaccine; IL-4 mutant; atopic dermatitis; contact hypersensitivity

Document Type: Research Article

Affiliations: 1: Department of Dermatology and Department of Immunology, Mie University, Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan 2: Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8507, Japan 3: Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki 305-0843, Japan

Publication date: 2009-06-01

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