Gene Ther 11(3):317-324 (2004).

Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice.

Sakamoto T, Miyazaki E, Aramaki Y, Arima H, Takahashi M, Kato Y, Koga M, Tsuchiya S.

School of Pharmacy, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo, Japan.

IL-10 is overexpressed in skin lesions of atopic dermatitis (AD) patients and believed to be an important factor in the pathogenesis of the disease. Thus the regulation of IL-10 production is a potential solution for immunotherapeutic intervention in AD. We examined the topical delivery of an antisense oligonucleotide for mouse IL-10 (AS6) and the therapeutic effect on the skin lesions of NC/Nga mice, a human AD model. Using an iontophoresis system, about 30% of the applied dose of AS6 penetrated the skin and was distributed in the epidermis and upper dermis. Topically delivered AS6 decreased the levels of mRNA and protein of IL-10 in the lesions of NC/Nga mice, with no effect on IL-4 levels. The dorsal lesions of NC/Nga mice disappeared with repeated topical application of AS6. Topically delivered AS6 showed an inhibitory effect on the production of IL-10 in the skin lesions of NC/Nga mice and had a therapeutic effect on the established dermatitis.