Bäumer W, Sülzle B, Weigt H, De Vries V C, Hecht M, Tschernig T, Kietzmann M
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany.
Br J Dermatol. 2005 Jul;153(1):136-44. doi: 10.1111/j.1365-2133.2005.06745.x.
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.
西洛司特、他克莫司以及雷帕霉素是治疗特应性皮炎和过敏性接触性皮炎等过敏性皮肤病的潜在药物。
比较磷酸二酯酶4抑制剂西洛司特与他克莫司和雷帕霉素在体外和体内的免疫调节作用。
在混合淋巴细胞反应（MLR）中测试西洛司特、他克莫司和雷帕霉素的体外作用。在体内，比较免疫调节药物在2,4-二异氰酸甲苯酯（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）功能。
西洛司特、他克莫司和雷帕霉素均能在MLR中抑制DC介导的T细胞活化。但已证明西洛司特的靶细胞是T细胞而非DC。在体内，这三种物质全身和局部联合给药均能在TDI激发后16小时显著抑制小鼠耳部肿胀。引流耳淋巴结重量、淋巴细胞计数和迁出的DC数量也有所减少。用西洛司特、他克莫司和雷帕霉素治疗的小鼠表皮中朗格汉斯细胞的密度相应高于用赋形剂治疗的小鼠。在TDI激发后对耳部组织进行的皮肤DC迁移试验中，发现所有三种物质均能在体外抑制DC迁移。
在过敏性接触性皮炎的激发阶段也会发生DC迁移至引流淋巴结的情况，这种迁移可受他克莫司和雷帕霉素影响，西洛司特的影响程度较小。
