Cilomilast, tacrolimus and rapamycin modulate dendritic cell function in the elicitation phase of allergic contact dermatitis
Cilomilast, tacrolimus and rapamycin modulate dendritic cell function in the elicitation phase of allergic contact dermatitis
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DOI：
10.1111/j.1365-2133.2005.06745.x
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发表时间：
2005-07-01
影响因子：
10.3
通讯作者：
Kietzmann, M
中科院分区：
文献类型：
--
作者：
Bäumer, W;Sülzle, B;Kietzmann, M
西洛司特、他克莫司和雷帕霉素是治疗特应性皮炎和变应性接触性皮炎等变应性皮肤病的潜在药物，为比较磷酸二酯酶4抑制剂西洛司特、他克莫司和雷帕霉素的体内外免疫调节作用，采用混合白细胞反应（MLR）检测了西洛司特、他克莫司和雷帕霉素的体外免疫调节作用。在体内，比较了免疫调节药物在甲苯-2，4-二异氰酸酯（TDI）诱导的过敏性炎症反应中的抑制作用，特别关注树突状细胞（DC）的功能，西洛司特，他克莫司和雷帕霉素都能够抑制MLR中DC介导的T细胞活化。但西洛司特的靶细胞是T细胞而不是DC。在体内，这三种物质中的每一种的全身和局部给药的组合在TDI激发后16小时显著抑制小鼠耳中的肿胀。引流耳淋巴结的重量、淋巴细胞计数和迁移的DC数量也减少。在用西洛司特、他克莫司和雷帕霉素处理的小鼠中，表皮中朗格汉斯细胞的密度相应地高于用媒介物处理的小鼠。所有这三种物质被发现抑制DC迁移离体在皮肤DC迁移试验进行耳组织后TDI challenge.DC迁移到引流淋巴结也发生在过敏性接触性皮炎的诱发阶段，这种迁移可以影响他克莫司和雷帕霉素，并在较小程度上，由西洛司特。
Cilomilast and tacrolimus as well as rapamycin are potential drugs for the treatment of allergic skin diseases like atopic dermatitis and allergic contact dermatitis.To compare the in vitro and in vivo immunomodulatory effects of the phosphodiesterase 4 inhibitor cilomilast with those of tacrolimus and rapamycin.The in vitro action of cilomilast, tacrolimus and rapamycin were tested in a mixed leucocyte reaction (MLR). In vivo, the inhibitory action of the immunomodulatory drugs was compared in the toluene-2,4-diisocyanate (TDI)-induced allergic inflammatory response with particular focus on dendritic cell (DC) function.Cilomilast, tacrolimus and rapamycin were all able to inhibit DC-mediated T-cell activation in a MLR. But it was demonstrated for cilomilast that the target cells are T cells rather than DC. In vivo, a combination of systemic and topical administration of each of these three substances significantly inhibited swelling in the murine ear 16 h after TDI challenge. There was also a reduction in the weight of the draining auricular lymph node, in lymphocyte cell count, and in the number of emigrated DC. The density of Langerhans cells in the epidermis was correspondingly higher in mice treated with cilomilast, tacrolimus and rapamycin than in those treated with vehicle. All three substances were found to inhibit DC migration ex vivo in a skin DC migration assay performed on ear tissue after TDI challenge.DC migration into the draining lymph node also takes place in the elicitation phase of allergic contact dermatitis and this migration can be influenced by tacrolimus and rapamycin, and, to a lesser extent, by cilomilast.