Establishment of tretments for patients with atopic dermatitis based on the immunological background

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The number of patients with severe atopic dermatitis (AD), who show an eosinophil-related late phase skin reaction and high levels of IgE, is increasing, although there is accumulating evidence revealing its pathomechanism. Ag-nonspecific immunosuppressants have been used for the treatment of AD. These therapeutic agents sometime cause the deterioration of the host immunologic defense. AD is associated with skewing of immune response towards Th2 phenotype. There is a real need for developing an antigen-specific treatment to selectively suppress Th2 cell-mediated responses. Oligodeoxynucleotides (ODN) containing CpG motifs have been highlighted as an immunomodulator that reduces Th2-mediated responses by biasing the T-cell response toward a Th1-dominant phenotype. To substantiate the effect of CpG ODN in the Th2-mediated skin inflammation, we introduced a unique cutaneous model of a protein-Ag-induced eosinophilic inflammation with increased levels of serum IgE in BALB/c by three-time i.p. priming with ovalbumin (OVA)/alum and following a week-OVA skin patching.. Intradermal administration of CpG ODN diminished the number of infiltrated eosinophils and IgE systemic response. Interestingly, intradermal CpG ODN at the site of OVA patching significantly augmented the inhibitory effects on both the eosinophil infiltration and IgE levels and more effective when administered with Ag. Our data suggest that a cutaneous administration of CpG ODN with Ag can work as a novel Ag-specific immunomodulator therapy to treat the cutaneous eosinophilic inflammation that can be found in patients with AD.