Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids)
Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids)
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DOI：
10.1016/s1567-5769(01)00059-5
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发表时间：
2001-06-01
影响因子：
5.6
通讯作者：
Goto, T
中科院分区：
文献类型：
--
作者：
Sakuma, S;Higashi, Y;Goto, T
他克莫司（FK 506）软膏在动物模型和临床试验中对特应性皮炎有显著疗效。研究了他克莫司对人外周血单核细胞（PBMC）产生特应性皮炎相关细胞因子（IL-2、IL-3、IL-4、IL-5、IFN-γ和GM-CSF）的抑制作用。我们构建了一种新的细胞因子产生系统，其中T细胞通过抗CD 3/CD 2或抗CD 3/CD 28抗体组合在体外直接刺激来活化。他克莫司抑制这些细胞因子的生产，这两个刺激。在一项与类固醇（二丙酸阿氯米松和戊酸倍他米松）在抗CD 3/CD 2系统中的比较研究中，他克莫司和两种类固醇均抑制Th 1细胞因子（IL-2、IFN-γ）、Th 3细胞因子（IL-4、IL-5）和IL 3、GM-CSF（由Th 1和Th 2产生）。他克莫司对细胞因子产生的抑制作用强于二丙酸阿氯米松，与戊酸倍他米松相当或更强。他克莫司的有效剂量（IC 50，0.02-0.11 ng/ml）几乎与Th 1和Th 2细胞因子相同，1 ng/ml他克莫司完全抑制所有细胞因子。这些结果表明，他克莫司抑制T细胞的过敏性细胞因子，他克莫司软膏是有效的特应性皮炎通过抑制细胞因子的产生。(C)2001 Elsevier Science B. V.保留所有权利。
Tacrolimus (FK506) ointment showed remarkable efficacy against atopic dermatitis in animal models and clinical trials. The suppressive effect of tacrolimus on the production of the cytokines involved in atopic dermatitis (IL-2, IL-3, IL-4, IL-5, IFN-gamma and GM-CSF) from human peripheral blood mononuclear cells (PBMC) was investigated. We constructed a new cytokine production system in which T cells are activated by direct stimulation in vitro with anti-CD3/CD2 or anti-CD3/CD28 antibody combination. Tacrolimus inhibited the production of these cytokines by both stimulations. In a comparative study with steroids (alclometasone dipropionate and betamethason valerate) in anti-CD3/CD2 system, tacrolimus and both steroids inhibited Th1 cytokines (IL-2, IFN-gamma:),Th3, cytokines (IL-4, IL-5) and IL3,GM-CSF (produced by both Th1 and Th2). The suppressive effect of tacrolimus on cytokine production was stronger than that of alclometasone dipropionate and equal to or stronger than that of betamethason valerate. The effective dose of tacrolimus (IC50, 0.02-0.11 ng/ml) is almost the same as for Th1 and Th2 cytokines, and 1 ng/ml of tacrolimus suppressed all cytokines completely. These results suggest that tacrolimus suppresses the allergic cytokines from T cells, and that tacrolimus ointment is effective against atopic dermatitis through the inhibition of cytokine production. (C) 2001 Elsevier Science B.V. All rights reserved.