ダニ抗原誘発性難治性皮膚炎に対する新規免疫調節薬FTY720とベタメタゾン軟膏併用療法の有用性 : NC/Ngaマウスを用いた検討  [in Japanese] THERAPEUTIC APPROACH TO MITE-INDUCED INTRACTABLE DERMATITIS USING NOVEL IMMUNOMODULATOR FTY720 (FINGOLIMOD) IN COMBINATION WITH BETAMETHASONE OINTMENT IN NC/Nga MICE  [in Japanese]

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Author(s)

    • 辻 琢己 Tsuji Takumi
    • 摂南大学薬学部病態医科学研究室 Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
    • 吉田 侑矢 Yoshida Yuya
    • 摂南大学薬学部病態医科学研究室 Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
    • 河野 武幸 Kohno Takeyuki
    • 摂南大学薬学部病態医科学研究室:生産開発科学研究所 Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University:Research Institute for Production and Development

Abstract

【背景と目的】難治性皮膚炎に対するFTY720とベタメタゾン軟膏併用療法の有用性をNC/Ngaマウスを用いて検討した.【方法】ダニ(Dermatophagoides farinae)抗原で難治性皮膚炎を発症させたNC/Ngaマウスをベタメタゾン吉草酸エステル軟膏(1日1回,週6回塗布), FTY720 (3mg/kg, 2日または3日に1回,週3回経口投与), FTY720+ベタメタゾン併用,軟膏基剤(1日1回,週6回塗布), FTY720+基剤併用およびプラセボで2週間治療し,治療効果を肉眼所見および組織化学的所見から評価した.【結果】FTY720+ベタメタゾン軟膏の併用により,本モデルの難治性皮膚炎は顕著に改善した.また,炎症に伴う表皮の肥厚の改善,集積マスト細胞数および浸潤T細胞数の減少が確認され,併用治療の有用性が組織化学的所見からも裏付けられた.【結語】FTY720とベタメタゾン軟膏の併用療法は,難治性ADに寛解を導入できる極めて有用な治療方法であることが示された.

Background: The increasing incidence and prevalence of atopic dermatitis (AD) have led to a requirement for new means to treat the disease. We investigated the therapeutic efficacy of the novel immunomodulator FTY720 (Fingolimod), alone and in combination with betamethasone valerate ointment, in the NC/Nga mouse model of mite-induced intractable dermatitis. Methods: Female NC/Nga mice in which dermatitis had been induced with Dermatophagoides farinae were divided into six groups: 1) a betamethasone group (betamethasone ointment, six times a week), 2) an FTY720 group (FTY720, orally, three times a week), 3) an FTY720 plus betamethasone ointment group, 4) an ointment base group (ointment base, six times a week), 5) an FTY720 plus ointment base group and 6) a placebo group (vehicle alone). The therapeutic efficacy was evaluated in terms of the severity of dermatitis and histochemical observations after two weeks of treatment. Results: Betamethasone treatment had little effect, confirming that the dermatitis was intractable. In the FTY720 plus betamethasone ointment group, the dermatitis was significantly improved as compared with the betamethasone ointment and placebo groups. This combination therapy also suppressed epidermal hypertrophy and accumulation of mast cells and CD 3^+ T-cells in dermis, all of which were observed in mice in which the dermatitis had become established. Conclusion: Our results strongly suggest that the combination of FTY720 plus betamethasone ointment is a promising candidate for treatment of intractable human AD.

Journal

  • Japanese Journal of Allergology

    Japanese Journal of Allergology 61(7), 948-958, 2012

    Japanese Society of Allergology

References:  31

Codes

  • NII Article ID (NAID)
    110009489268
  • NII NACSIS-CAT ID (NCID)
    AN00012583
  • Text Lang
    JPN
  • Article Type
    ART
  • ISSN
    0021-4884
  • NDL Article ID
    023937629
  • NDL Call No.
    Z19-32
  • Data Source
    CJP  NDL  NII-ELS  J-STAGE 
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