Noguchi Atsushi, Tominaga Mitsutoshi, Takahashi Nobuaki, Matsuda Hironori, Kamata Yayoi, Umehara Yoshie, Ko Kyi Chan, Suga Yasushi, Ogawa Hideoki, Takamori Kenji
Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan; Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
J Dermatol Sci. 2017 Apr;86(1):54-62. doi: 10.1016/j.jdermsci.2016.12.015. Epub 2016 Dec 24.
Topical corticosteroid and calcineurin inhibitor have similar therapeutic benefits in atopic dermatitis (AD), but the differences in therapeutic mechanisms of action of these agents against AD symptoms are not fully understood.
This study was performed to examine the different effects of topical betamethasone valerate (BMV), clobetasol propionate (CBP), and tacrolimus (TAC) on itch-related behavior and dermatitis in NC/Nga mice with AD-like symptoms.
AD-like dermatitis was induced in the dorsal skin of NC/Nga mice by repeated topical application of Dermatophagoides farinae body (Dfb) ointment twice weekly for three weeks. Mice with dermatitis scores over 5 were divided into five groups with equal dermatitis scores and treated with BMV, CBP, TAC, or Vaseline (Vas) once daily for two consecutive days, or were not treated (NT). Scratching behavior was analyzed using a SCLABA-Real system. Transepidermal water loss (TEWL) before and after treatment was measured using a Tewameter TM210. Skin collected from each group was analyzed histologically.
After the second treatment, dermatitis showed significantly greater improvement in the CBP and TAC-treated groups than in the Vas-treated and NT groups. The numbers of scratching bouts were significantly lower in CBP and TAC-treated mice than in Vas-treated mice. TEWL was significantly lower in TAC-, but not in CBP-, treated mice than in Vas-treated mice. Immunohistochemical examination showed that BMV, CBP and TAC did not reduce the increased densities of epidermal protein gene product 9.5- and substance P-immunoreactive fibers. The numbers of dermal CD4-immunoreactive T cells were significantly lower in BMV and CBP-treated mice than in Vas-treated and NT mice. The numbers of dermal eosinophils were significantly lower in BMV, CBP and TAC-treated mice than in Vas-treated and NT mice, with CBP showing the strongest effect. CBP significantly reduced epidermal thickness compared with Vas and NT. There were no significant differences in the numbers of interleukin-31-immunoreactive cells and mast cells, or in expression of epidermal thymic stromal lymphopoietin among all five groups.
The therapeutic potency of TAC against AD-like symptoms, including pruritus, is equal to that of the corticosteroid CBP. Epidermal innervation of sensory nerves itself might not be related to the therapeutic effects of topical tacrolimus and corticosteroids in its early phase.
外用糖皮质激素和钙调神经磷酸酶抑制剂在特应性皮炎（AD）中具有相似的治疗效果，但这些药物针对AD症状的治疗作用机制差异尚未完全明确。
本研究旨在探讨外用戊酸倍他米松（BMV）、丙酸氯倍他索（CBP）和他克莫司（TAC）对具有AD样症状的NC/Nga小鼠瘙痒相关行为和皮炎的不同影响。
通过每周两次重复外用粉尘螨虫体（Dfb）软膏，持续三周，诱导NC/Nga小鼠背部皮肤发生AD样皮炎。皮炎评分超过5分的小鼠被分为皮炎评分相等的五组，连续两天每天分别用BMV、CBP、TAC或凡士林（Vas）治疗一次，或不进行治疗（NT）。使用SCLABA-Real系统分析搔抓行为。使用Tewameter TM210测量治疗前后的经表皮水分流失（TEWL）。对每组收集的皮肤进行组织学分析。
第二次治疗后，CBP和TAC治疗组的皮炎改善程度明显大于Vas治疗组和NT组。CBP和TAC治疗的小鼠搔抓次数明显低于Vas治疗的小鼠。TAC治疗的小鼠TEWL明显低于Vas治疗的小鼠，但CBP治疗的小鼠并非如此。免疫组织化学检查显示，BMV、CBP和TAC并未降低表皮蛋白基因产物9.5和P物质免疫反应性纤维密度的增加。BMV和CBP治疗的小鼠真皮中CD4免疫反应性T细胞数量明显低于Vas治疗组和NT组小鼠。BMV、CBP和TAC治疗的小鼠真皮中嗜酸性粒细胞数量明显低于Vas治疗组和NT组小鼠，CBP的效果最强。与Vas和NT相比，CBP显著降低了表皮厚度。五组之间白细胞介素-31免疫反应性细胞和肥大细胞数量，或表皮胸腺基质淋巴细胞生成素表达均无显著差异。
TAC对包括瘙痒在内的AD样症状的治疗效力与糖皮质激素CBP相当。感觉神经的表皮神经支配本身可能与其早期外用他克莫司和糖皮质激素的治疗效果无关。
