Topical Application of FK506 (Tacrolimus) Ointment Inhibits Mite Antigen-Induced Dermatitis by Local Action in NC/Nga Mice

Abstract

Background: FK506 ointment (tacrolimus ointment, protopic) is a new drug therapeutically effective for patients with atopic dermatitis (AD). However, the mechanism of action of FK506 ointment on AD is not fully understood. Methods: We examined the effect of FK506 ointment on mite antigen-induced dermatitis in NC/Nga mice. Clinical symptoms and ear thickness were recorded, and histopathological studies and in vitro analyses were performed. Results: Topical application of FK506 ointment (0.03–0.3%) suppressed the development of dermatitis. In the lesional skin, both interleukin (IL)-4 and interferon (IFN)-γ were detected, even though the IL-4+/IFN-γ– T helper 2 (Th2) population was predominant in the regional lymph nodes (LNs). Topical application of FK506 treatment reduced the elevated level of both IL-4 and IFN-γ in the skin, but did not decrease the expansion of the Th2 population in the LNs. Conclusions: Topical application of FK506 ointment suppresses dermatitis by inhibiting the activation of inflammatory cells locally, without systemic immune suppression, in this AD model.

Evaluation of FITC-Induced Atopic Dermatitis-Like Disease in NC/Nga Mice and BALB/c Mice Using Computer-Assisted Stereological Toolbox, a Computer-Aided Morphometric System

“…In contrast to the findings of others [9, 16], our results showed rather unexpectedly that neither the NC/Nga nor the BALB/c mice responded to treatment with betamethasone or tacrolimus with a reduction of the cellular infiltrate. In these experiments, challenge and treatment were given at the same time; consequently, the mice may develop an immunological response to the treatment, thus explaining the inflammatory response observed following corticosteroid treatment.…”

A murine model of epicutaneous protein sensitization is useful to study efficacies of topical drugs in atopic dermatitis

“…Current topical treatment possibilities for AD are topical corticosteroids as a standard treatment and topical calcineurin inhibitors (macrolide immunosuppressants) such as tacrolimus or pimecrolimus as a second-line therapy [1]. Previously, only spontaneous mouse models of AD have been used to investigate topical drugs in AD [19,20]. Here we show that our mouse model of AD caused by repeated epicutaneous ovalbumin (OVA) and SEB exposures is valuable and repeatable model to test topical drugs in AD.…”

Inhibition of atopic dermatitis by topical application of silymarin in NC/Nga mice

“…NC/Nga mouse model has been considered as one of the most valuable mouse model representing human AD [5,18,19]. This model has been used for the evaluation of drug candidates developed for the treatment of AD [20,21]. Previously, we established a modified NC/Nga mouse model and suggested that this model might be a useful tool to evaluate drug candidates of AD [16].…”