Topical Application of Josamycin Inhibits Development of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice.

Abstract

Patients with atopic dermatitis (AD) have superficial skin colonization by Staphylococcus aureus and an increased number of T helper type 2 (Th2) cells in their peripheral blood. Our previous study showed that josamycin, a macrolide antibiotic, had excellent bactericidal activity against S. aureus strains isolated from AD patients and simultaneously inhibited Th1 and Th2 cell development mediated by Langerhans cells. The purpose of the present study was to evaluate the effect of topical application of josamycin on AD-like skin lesions in NC/Nga mice. Josamycin (0.1%) was topically administered to NC/Nga mice with AD-like skin lesions induced by 2, 4, 6-trinitrochlorobenzene (TNCB). The therapeutic effects of josamycin were assessed by measurement of the skin severity scores, histological changes in the lesioned skin, serum levels of total IgE, and expression of interferon (IFN)-γ and interleukin (IL)-4 in lymph nodes and skin lesions. Topical treatment with josamycin significantly suppressed the increase in the skin severity score in NC/Nga mice. This suppressive effect was equal to that of betamethasone, and was associated with a decrease in the density of cellular infiltration into the dermis, the mast cell count in the dermis and the serum IgE level. Furthermore, topical application of josamycin reduced the expression of IFN-γ and IL-4 in auricular lymph node cells and the skin lesions. The present results show that topical application of josamycin inhibits the development of AD-like skin lesions in NC/Nga mice. This suggests that topical application of josamycin to AD lesions colonized by S. aureus would be beneficial for control of AD by acting on superficially located S. aureus and by inhibiting the development of Th1 and Th2 cells.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.