title: Therapeutic approach to steroid-resistant dermatitis using novel immunomodulator FTY720 (Fingolimod) in combination with betamethasone ointment in NC/Nga mice.
abstract: The therapeutic efficacy of the novel immunomodulator FTY720 (Fingolimod), alone and in combination with betamethasone ointment, was examined in the NC/Nga mouse model of spontaneous steroid-resistant dermatitis. Male NC/Nga mice which had developed severe dermatitis were divided into six groups: 1) a biweekly betamethasone group (betamethasone ointment, twice a week), 2) a daily betamethasone group (betamethasone ointment, six times a week), 3) an FTY720 group (FTY720, orally, three times a week), 4) a biweekly combination group (oral FTY720 plus betamethasone ointment, twice a week), 5) a daily combination group (oral FTY720 plus betamethasone ointment, six times a week) and 6) a placebo group (vehicle alone). The therapeutic efficacy was evaluated in terms of severity of dermatitis, epidermal hypertrophy, accumulation and degranulation of mast cells and infiltrated CD3+ T cells into the dermis after 4 weeks of treatment. Biweekly and daily betamethasone treatments had little effect, confirming that the dermatitis was steroid-resistant. In the FTY720 and biweekly combination groups, the dermatitis showed no marked improvement. In the daily combination group, the dermatitis was significantly (p<0.05, Mann-Whitney U-test) improved as compared with the FTY720 group, biweekly and daily betamethasone groups and placebo group. Further, epidermal hypertrophy and accumulation of mast cells were suppressed. Therefore, combination therapy with FTY720 and daily betamethasone ointment is a promising candidate for treatment of steroid-resistant atopic dermatitis.
authors.affiliation: Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Rumi
authors.initials: R
authors.lastname: Iwatsuki
authors.forename: Mariko
authors.initials: M
authors.lastname: Inoue
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Fujita
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Kohno
mesh_terms: D000818:Animals; D001203:Ascomycota / Q000737:chemistry; D001623:Betamethasone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001688:Biological Products / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003872:Dermatitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004351:Drug Resistance / Q000187:drug effects*; D004817:Epidermis / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D000068876:Fingolimod Hydrochloride; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006984:Hypertrophy / Q000188:drug therapy; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008517:Phytotherapy; D011409:Propylene Glycols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013256:Steroids; D016896:Treatment Outcome
chemical_list: D001688:Biological Products; D005938:Glucocorticoids; D007155:Immunologic Factors; D011409:Propylene Glycols; D013256:Steroids; D001623:Betamethasone; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine