Sasakawa Tatsuya, Higashi Yasuyuki, Sakuma Shozo, Hirayama Yoshitaka, Sasakawa Yuka, Ohkubo Yoshitaka, Mutoh Seitaro
Department of Immunology and Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co Ltd, Osaka, Japan.
Int Arch Allergy Immunol. 2004 Jan;133(1):55-63. doi: 10.1159/000076128. Epub 2004 Jan 12.
FK506 ointment (tacrolimus ointment, protopic) is a new drug therapeutically effective for patients with atopic dermatitis (AD). However, the mechanism of action of FK506 ointment on AD is not fully understood.
We examined the effect of FK506 ointment on mite antigen-induced dermatitis in NC/Nga mice. Clinical symptoms and ear thickness were recorded, and histopathological studies and in vitro analyses were performed.
Topical application of FK506 ointment (0.03-0.3%) suppressed the development of dermatitis. In the lesional skin, both interleukin (IL)-4 and interferon (IFN)-gamma were detected, even though the IL-4+/IFN-gamma- T helper 2 (Th2) population was predominant in the regional lymph nodes (LNs). Topical application of FK506 treatment reduced the elevated level of both IL-4 and IFN-gamma in the skin, but did not decrease the expansion of the Th2 population in the LNs.
Topical application of FK506 ointment suppresses dermatitis by inhibiting the activation of inflammatory cells locally, without systemic immune suppression, in this AD model.
FK506软膏(他克莫司软膏,普特彼)是一种治疗特应性皮炎(AD)有效的新药。然而,FK506软膏对AD的作用机制尚未完全明确。
我们研究了FK506软膏对NC/Nga小鼠螨抗原诱导性皮炎的影响。记录临床症状和耳部厚度,并进行组织病理学研究和体外分析。
局部应用FK506软膏(0.03 - 0.3%)可抑制皮炎的发展。在病变皮肤中,检测到白细胞介素(IL)-4和干扰素(IFN)-γ,尽管在局部淋巴结(LN)中IL-4+/IFN-γ-T辅助细胞2(Th2)群体占主导。局部应用FK506治疗可降低皮肤中IL-4和IFN-γ的升高水平,但并未减少LN中Th2群体的扩增。
在该AD模型中,局部应用FK506软膏通过局部抑制炎症细胞的激活来抑制皮炎,而无全身免疫抑制作用。