Reduced dermal infiltration of cytokineexpressing inflammatory cells in atopic dermatitis after short-term topical tacrolimus treatment
Reduced dermal infiltration of cytokineexpressing inflammatory cells in atopic dermatitis after short-term topical tacrolimus treatment
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DOI：
10.1016/j.jaci.2004.05.066
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发表时间：
2004-10-01
影响因子：
14.2
通讯作者：
Simon, HU
中科院分区：
文献类型：
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作者：
Simon, D;Vassina, E;Simon, HU
背景：多项临床研究显示，外用钙调神经磷酸酶抑制剂可有效治疗特应性皮炎 (AD)。它们针对控制基因表达，特别是细胞因子表达的信号通路。 目的：我们检查了 10 名 AD 患者皮损中的细胞浸润，并表征了使用他克莫司软膏短期局部治疗前后浸润细胞表达的细胞因子模式。方法：检查皮肤活检的组织学改变（苏木精和伊红染色）、细胞炎症浸润的组成他克莫司治疗开始前以及开始后 1 周和 3 周时（免疫荧光）和细胞因子表达（核糖核酸酶保护测定、ELISA、免疫荧光）。为了进行比较，对非病变 AD 和正常皮肤的活检进行了分析。通过分析外周血白细胞（免疫荧光）以及体外刺激的泛 T 细胞细胞因子产生 (ELISA) 来评估全身免疫效应。 结果：所有患者的皮肤病变均显着改善，与真皮中海绵组织增生、棘皮症和细胞浸润密度明显消退相关。最后一个是 T 细胞、B 细胞和嗜酸性粒细胞浸润减少的结果。相比之下，肥大细胞的数量没有变化。此外，治疗后CD4(+) T细胞中T(H)2细胞因子IL-5、IL-10和IL-13的表达降低。有趣的是，他克莫司治疗还与表达 T(H)1 细胞因子 IFN-γ 的 CD8(+) T 细胞减少有关。此外，治疗后表皮CD1a(+)树突状细胞的数量增加。在外周血中，观察到粒细胞（嗜酸性粒细胞和中性粒细胞）减少，但淋巴细胞亚群的分布没有变化。结论：外用他克莫司治疗对 AD 皮肤具有抗炎作用，表现为表达细胞因子的炎症细胞浸润减少。没有获得药物诱导的全身免疫抑制的证据。
Background: In several clinical studies, topical calcineurin inhibitors have been shown to be effective in the treatment of atopic dermatitis (AD). They target signaling pathways that control gene expression, particularly the expression of cytokines.Objective: We examined the cellular infiltrate in skin lesions of 10 patients with AD and characterized the cytokine pattern expressed by the infiltrating cells before and after short-term topical therapy with tacrolimus 1% ointment.Methods: Skin biopsies were examined for histologic alterations (hematoxylin and eosin staining), composition of the cellular inflammatory infiltrate (immunofluorescence), and cytokine expression (ribonuclease protection assay, ELISA, immunofluorescence) before as well as 1 and 3 weeks after initiation of tacrolimus therapy. For comparison, biopsies from nonlesional AD and normal skin were analyzed. Systemic immunologic effects were assessed by analyzing peripheral blood leukocytes (immunofluorescence) as well as in vitro stimulated pan-T-cell cytokine production (ELISA).Results: All patients showed a significant improvement of their skin lesions associated with a marked regression of spongiosis, acanthosis, and density of the cellular infiltrate in the dermis. The last was a result of reduced infiltration of T cells, B cells, and eosinophils. In contrast, the numbers of mast cells did not change. Moreover, the expression of the T(H)2 cytokines IL-5, IL-10, and IL-13 in CD4(+) T cells was reduced after therapy. Interestingly, tacrolimus therapy was also associated with a reduction of CD8(+) T cells expressing the T(H)1 cytokine IFN-gamma. Furthermore, the numbers of epidermal CD1a(+) dendritic cells increased after treatment. In the peripheral blood, a decrease of granulocytes (eosinophils and neutrophils) but no changes in the distribution of lymphocyte subpopulations were noticed.Conclusion: Topical tacrolimus treatment has antiinflammatory effects on AD skin as indicated by reduced infiltration of cytokine expressing inflammatory cells. No evidence for drug-induced systemic immunosuppression was obtained.