Tsuji Takumi, Yoshida Yuya, Fujita Tetsuro, Kohno Takeyuki
Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University.
Arerugi. 2012 Jul;61(7):948-58.
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.
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.
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 CD3+T-cells in dermis, all of which were observed in mice in which the dermatitis had become established.
Our results strongly suggest that the combination of FTY720 plus betamethasone ointment is a promising candidate for treatment of intractable human AD.
特应性皮炎(AD)发病率和患病率的不断上升,促使人们需要新的治疗方法。我们在尘螨诱导的难治性皮肤炎NC/Nga小鼠模型中,研究了新型免疫调节剂FTY720(芬戈莫德)单独使用以及与戊酸倍他米松软膏联合使用的治疗效果。
用粉尘螨诱导皮肤炎的雌性NC/Nga小鼠被分为六组:1)倍他米松组(倍他米松软膏,每周六次),2)FTY720组(FTY720,口服,每周三次),3)FTY720加戊酸倍他米松软膏组,4)软膏基质组(软膏基质,每周六次),5)FTY720加软膏基质组和6)安慰剂组(仅赋形剂)。治疗两周后,根据皮肤炎的严重程度和组织化学观察结果评估治疗效果。
倍他米松治疗效果不佳,证实该皮肤炎难治。在FTY720加戊酸倍他米松软膏组中,与倍他米松软膏组和安慰剂组相比,皮肤炎有显著改善。这种联合治疗还抑制了表皮增生以及肥大细胞和CD3 + T细胞在真皮中的积聚,而在已患皮肤炎的小鼠中均观察到了这些现象。
我们的结果强烈表明,FTY720加戊酸倍他米松软膏的联合治疗有望成为治疗难治性人类AD的方法。