Clarithromycin Inhibits the Development of Dermatitis in NC/Nga Mice

Abstract

Background: Colonization of Staphylococcus aureus on the skin is one of the exacerbating factors of atopic dermatitis (AD). Reduction of bacterial colonization in these lesions was reported to be effective for the treatment of subjects with AD. Clinical trials have demonstrated the efficacy of FK-506 (an immunosuppressive macrolide) ointment for AD, and many case reports have been published regarding its positive effects for other inflammatory skin diseases. Clarithromycin (CAM) is a macrolide antibiotic with immunological effects. One patient with AD was treated effectively with oral CAM for Helicobacter pylori infection. NC/Nga (NC) mice have recently been recognized to be a model of AD. Methods: We examined the effects of CAM on the development of dermatitis, infiltration of mast cells and MHC class II-positive cells in the skin and the colonization of S. aureus on the skin of NC mice. CAM was compared with cefaclor, an antibiotic with no immunological effects. Results: CAM suppressed the development of dermatitis at 5 and 6 weeks to a statistically significant degree, and these effects gradually weakened, but the severity of the dermis of CAM-treated mice was milder than in control mice. Dexamethasone was effective in the case of development of dermatitis at 5 weeks. These effects gradually weakened, and the difference between dexamethasone-treated mice and control mice disappeared. The severity of the skin lesions in CAM-treated mice was the lowest of the three groups at 9 weeks of observation. Histological analyses revealed that infiltration of inflammatory cells, especially degranulated mast cells and MHC class II-positive cells, was significantly reduced. Thickening of the epidermis and hyperkeratosis in CAM-treated mice were less than in control mice. CAM and cefaclor completely inhibited S. aureus on the skin of NC mice, for all experimental periods. Dexamethasone provided inhibition at 5 weeks, but eventually the difference between dexamethasone-treated mice and control mice disappeared. Conclusions: CAM inhibited the development of dermatitis for the first half of the experimental period in NC mice as a result of antibacterial and immunological effects. Our data show that CAM can be an effective antibiotic for AD with respect to delaying the development of dermatitis.