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)-γ 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-γ
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-γ). These findings suggest that RPM and/or MPA may be promising topical therapeutic candidates for the treatment of AD.