Effect of Tacrolimus Hydrate (FK506) Ointment on Spontaneous Dermatitis in NC/Nga Mice

Abstract

The effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga (NC) mice was examined. FK506 ointment (0.1-1%) suppressed the development of dermatitis and was also therapeutically effective against established dermatitis. Increases in CD4-positive T cells (helper T cells), mast cells, eosinophils and immunostaining of interleukin (IL)-4, IL-5 and IgE were confirmed in the skin of the NC mice, and FK506 ointment suppressed all of these changes. Increased plasma IgE was also confirmed in the NC mice, and treatment with FK506 ointment reduced the plasma IgE level. These results suggested that FK506 suppressed the dermatitis by inhibiting the activation of inflammatory cells and by blocking the cytokine network in the skin of the NC mice. The commercially available steroid ointments showed only marginal effect on the development of dermatitis and showed some signs of side effects such as alopecia or atrophy of the skin. The effect of the steroids might have been masked by these side effects because the steroids showed similar inhibitory effects on the skin histopathological changes and the increase of plasma IgE. From these results, FK506 ointment can be expected to be a useful drug for atopic dermatitis.

Prevention and regression of atopic dermatitis by ointment containing NF-kB decoy oligodeoxynucleotides in NC/Nga atopic mouse model

“…The importance of these cytokines in atopic dermatitis was confirmed by the observation that corticosteroids and tacrolimus (FK-506) inhibit NF-kB activation. 22,23 In addition to the decrease in inflammatory cytokines, the improvement of dysregulated apoptosis in skin-homing cells may also contribute to the development and persistence of atopic dermatitis. 24 More recently, the importance of NFkB was proved by the observation that IkB␣ deficiency resulted in a sustained NF-kB response and severe widespread dermatitis in mice.…”

“…Topically active macrolide immunosuppressants, such as ascomycin and tacrolimus appear to provide comparable therapeutic potency. 22,23 Although the data from ongoing studies will be crucial in determining the safety of these agents in the long term, and also their place within the current therapeutic armamentarium available for patients with atopic dermatitis, these agents still have potential side-effects, such as systemic absorption. In contrast, NF-kB decoy ODN only exert local pharmacological effects for the following reasons: (1) ODN in serum were rapidly destroyed (within several hours), leading to a lack of systemic effects.…”

Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice

“…Currently, on the other hand, topical applications of corticosteroids and tacrolimus (FK-506) are commonly used to treat AD, through immunosuppressive effects that are based on the inhibition of NF-kB activation. 31,32 In addition, Nakamura et al 33 reported that a single topical delivery of NF-kB decoy ODNs significantly regressed atopic dermatitis in NC/Nga mice. TARC is the primary chemokine in ADlike lesions of NC/Nga mice, 9 and TARC serum levels are closely related to disease activity in human AD.…”

Citric acid inhibits a bacterial ceramidase and alleviates atopic dermatitis in an animal model

“…8,9 It is reported that mast cells are increased in the dermis with dermatitis and that tacrolimus hydrate improves the spontaneous dermatitis in NC/Nga mice. 8 Furthermore, we have recently reported that ceramidastin efficiently reduces the mast cells in the mouse model.…”

“…8,9 It is reported that mast cells are increased in the dermis with dermatitis and that tacrolimus hydrate improves the spontaneous dermatitis in NC/Nga mice. 8 Furthermore, we have recently reported that ceramidastin efficiently reduces the mast cells in the mouse model. 7 As shown in Figure 3, the application of the Pseudomonas ceramidase on the back of mice resulted in the significant increase in mast cells in the dermis.…”