چکیده (انگلیسی):

Background: The increasing incidence and prevalence of atopic dermatitis (AD) demands new therapeutic
approaches for treating the disease.We investigated the therapeutic efficacy of immunomodulator
FTY720 ointment (fingolimod) for mite-induced intractable AD using an NC/Nga mouse model.
Methods: Female NC/Nga mice that developed severe AD were divided into four groups: (1) FTY720
(0.001% FTY720 ointment), (2) tacrolimus (tacrolimus hydrate ointment) (3) betamethasone (betamethasone
ointment), and (4) ointment base (hydrophilic petrolatum), all of which received treatment six
times per week. Therapeutic efficacy after two weeks was evaluated in terms of AD severity, histochemical
observations (epidermal hypertrophy, mast cell accumulation, and CD3þ T cell infiltration),
transepidermal water loss (TEWL), and epidermal barrier function (filaggrin expression).
Results: Betamethasone treatment showed little effect, confirming that the AD was intractable. In the
FTY720 group, AD improved significantly compared with the ointment base group, as did epidermal
hypertrophy, mast cell accumulation, and CD3þ T cell infiltration. In contrast, AD in the tacrolimus and
betamethasone groups did not improve significantly, nor did epidermal hypertrophy or mast cell
accumulation. Furthermore, in the FTY720 group, TEWL decreased significantly compared with the
ointment base group, and filaggrin expression significantly increased compared with the betamethasone
and ointment base groups.
Conclusions: FTY720 ointment is a promising candidate for treatment of intractable AD. These findings
also provide the first evidence that FTY720 ointment ameliorates epidermal barrier function.