The Catholic University of Korea, Seoul, Korea.
Am J Rhinol Allergy. 2012 Mar-Apr;26(2):e71-5. doi: 10.2500/ajra.2012.26.3743.
The management of allergic rhinitis (AR) encompasses education, pharmacotherapy, immunotherapy, and surgery. FK506 (tacrolimus) is an immunosuppressant that inhibits allergic reactions. The purpose of this study was to reveal whether FK506 treatment reduces allergic inflammation in an AR mouse model and to elucidate the mechanisms.
Forty mice were divided into four groups: control, AR, FK (FK506), and dexamethasone (DEX). All mice except for the control group were sensitized by an i.p. injection of ovalbumin (OVA). After sensitization, the FK and DEX groups were treated with FK506 and DEX intranasally. All sensitized mice were challenged intranasally with OVA. Allergic symptoms and tissue eosinophil counts were recorded. Interleukin (IL)-5, interferon gamma, and IL-10 levels in nasal lavage fluid (NALF) and serum OVA-specific IgE levels were measured. T-bet, GATA-3, and Foxp3 mRNA expression in splenic mononuclear cells were determined by real-time polymerase chain reaction.
In the FK group and DEX group, allergic symptoms, serum OVA-specific IgE, tissue eosinophil counts, IL-5 in NALF, and GATA-3 mRNAs expression decreased (p < 0.05), and IL-10 in NALF and Foxp3 mRNAs expression increased compared with the AR group (p < 0.05). No significant difference was observed between the FK group and the DEX group.
These results suggest that topical FK506 may reduce allergic inflammation and have potency equal to DEX in the AR model. This mechanism may involve not only Th2 cells but also regulatory T cells. Additional studies are needed on FK506, but in the future, we can consider FK506 as an alternative to topical steroids in the treatment of AR.
变应性鼻炎（AR）的治疗包括教育、药物治疗、免疫治疗和手术。FK506（他克莫司）是一种抑制过敏反应的免疫抑制剂。本研究旨在揭示 FK506 治疗是否会减少 AR 小鼠模型中的过敏炎症，并阐明其机制。
40 只小鼠分为四组：对照组、AR 组、FK（FK506）组和地塞米松（DEX）组。除对照组外，所有小鼠均通过腹腔注射卵清蛋白（OVA）致敏。致敏后，FK 和 DEX 组用 FK506 和 DEX 经鼻给药。所有致敏小鼠均用 OVA 经鼻激发。记录过敏症状和组织嗜酸性粒细胞计数。测量鼻洗液（NALF）中的白细胞介素（IL）-5、干扰素γ和 IL-10 水平以及血清 OVA 特异性 IgE 水平。通过实时聚合酶链反应测定脾单核细胞中的 T-bet、GATA-3 和 Foxp3 mRNA 表达。
在 FK 组和 DEX 组中，与 AR 组相比，过敏症状、血清 OVA 特异性 IgE、组织嗜酸性粒细胞计数、NALF 中的 IL-5 和 GATA-3 mRNA 表达降低（p<0.05），而 NALF 中的 IL-10 和 Foxp3 mRNA 表达增加（p<0.05）。FK 组和 DEX 组之间无显著差异。
这些结果表明，局部 FK506 可能减轻 AR 模型中的过敏炎症，且其疗效与 DEX 相当。该机制可能不仅涉及 Th2 细胞，还涉及调节性 T 细胞。需要对 FK506 进行更多研究，但在未来，我们可以考虑将 FK506 作为 AR 治疗中局部类固醇的替代药物。
