Yamamoto Mina, Haruna Takayo, Yasui Kiyoshi, Takahashi Hisashi, Iduhara Miho, Takaki Shigeki, Deguchi Masashi, Arimura Akinori
Discovery Research Laboratory, Shionogi & Co., LTD., Osaka, Japan.
Allergol Int. 2007 Jun;56(2):139-48. doi: 10.2332/allergolint.O-06-458. Epub 2007 May 1.
Atopic dermatitis is a chronically relapsing inflammatory skin disease. Animal models induced by relevant allergens play a very important role in the elucidation of the disease. The patients with atopic dermatitis are highly sensitized with mite allergens such as Dermatophagoides farinae (Df). Therefore, in the present study, we tried to develop a novel model for atopic dermatitis by repeated application with Df extract ointment.
Df extract ointment was repeatedly applied to the back of NC/Nga mice together with barrier disruption. Atopic dermatitis-like skin lesions were evaluated by dermatitis scores, skin histology and immunological parameters. The effect of corticosteroid and calcineurin inhibitor was also examined.
Repeated application of Df extract ointment caused rapid increase in dermatitis scores. Clinical (skin dryness, erythema, edema and erosion) and histological symptoms (dermal and epidermal thickening, hyperkeratosis, parakeratosis and inflammatory cell infiltration) in this model were very similar to those in human atopic dermatitis. Serum total and Df-specific IgE levels were elevated in this model compared with normal mice, and draining lymph node cells isolated from the mice that exhibited dermatitis produced significant amounts of interleukin-5, interleukin-13 and interferon-gamma after re-stimulation with Df. Furthermore, current first-line drugs for the treatment of human atopic dermatitis, corticosteroid and tacrolimus ointments, were effective against the clinical and histological symptoms in this model.
These results suggest that the model we have established is useful for not only elucidating the pathogenesis of atopic dermatitis but also for evaluating therapeutic agents.
特应性皮炎是一种慢性复发性炎症性皮肤病。由相关过敏原诱导的动物模型在该疾病的阐明中起着非常重要的作用。特应性皮炎患者对螨类过敏原如粉尘螨（Df）高度敏感。因此，在本研究中，我们试图通过反复涂抹Df提取物软膏来建立一种新的特应性皮炎模型。
将Df提取物软膏与屏障破坏一起反复涂抹于NC/Nga小鼠背部。通过皮炎评分、皮肤组织学和免疫学参数评估特应性皮炎样皮肤病变。还检测了皮质类固醇和钙调神经磷酸酶抑制剂的效果。
反复涂抹Df提取物软膏导致皮炎评分迅速增加。该模型中的临床症状（皮肤干燥、红斑、水肿和糜烂）和组织学症状（真皮和表皮增厚、角化过度、不全角化和炎症细胞浸润）与人类特应性皮炎非常相似。与正常小鼠相比，该模型中血清总IgE水平和Df特异性IgE水平升高，并且从表现出皮炎的小鼠中分离出的引流淋巴结细胞在用Df重新刺激后产生大量白细胞介素-5、白细胞介素-13和干扰素-γ。此外，目前用于治疗人类特应性皮炎的一线药物皮质类固醇和他克莫司软膏对该模型中的临床和组织学症状有效。
这些结果表明，我们建立的模型不仅有助于阐明特应性皮炎的发病机制，还可用于评估治疗药物。
