Effects of topically applied rapamycin and mycophenolic acid on TNCB-induced atopic dermatitis-like skin lesions in NC/Nga mice

Abstract

Rapamycin (RPM) and mycophenolic acid (MPA) are immunosuppressive drugs approved for use in preventing transplant rejection. These drugs have also been used in the field of dermatology as glucocorticoid sparing agents for autoimmune and inflammatory disorders such as atopic dermatitis (AD). The aim of this study was to investigate the therapeutic effect of topically applied RPM and/or MPA on AD-like skin lesions in NC/Nga mice. RPM (0.04% - 4%), MPA (0.2% - 5%), and formulations of both agents at various ratios were administrated topically to NC/Nga mice with 2-chloro-1,3,5-trinitrobenzene (TNCB)-induced AD-like skin lesions. The therapeutic effects of topical RPM, MPA, and the mixed formulations in TNCB-treated NC/Nga mice were assessed by measuring skin severity scores, ear thickness, and histological changes in the lesioned skin including mast cell count and total serum IgE levels. Expression of interleukin (IL)-4, and interferon (IFN)-gamma was also assessed. Topical 4% RPM and/or 1% MPA treatment significantly improved clinical signs of AD such as erythema, edema, excoriation, and dryness on day 29 (P < 0.05). In addition, 4% RPM, 1% MPA, and the mixed formulations significantly decreased epidermal thickening, dermal edema, and cellular infiltration into the dermis compared with the vehicle. RPM (4%) and/or MPA (1%) significantly reduced the expression of IL-4 and IFN-gamma mRNA and protein levels compared with the vehicle (P < 0.05). No significant change in the levels of total serum IgE was induced by topical 4% RPM and/or 1% MPA. The present results demonstrated that topical 4% RPM and/or 1% MPA improved TNCB-induced AD-like lesions of NC/Nga mice by suppressing expression of Th2-related cytokines (IL-4) and Th1-related cytokines (IFN-gamma). These findings suggest that RPM and/or MPA may be promising topical therapeutic candidates for the treatment of AD. (C) 2015 Elsevier B.V. All rights reserved.