Formation and localization of allergy and biomodulation by dendritic cells-cytokines and adhesion molecules-

我们已经检测了1)特应性皮炎(AD)患者的血清IL-4和IL-5水平，2)外周血单个核细胞内细胞因子的变化，以及3)外周血中血清标志物的时间变化。我们发现1)血清IL-4和IL-5水平不是AD的有用标志物，2)单核细胞流式细胞术分析揭示了AD患者以Th2为主的模式，3)AD患者的血清标志物如ECP和SELAM-1迅速下降。在1997年的项目中，我们进一步研究了血清ECP、SELAM-1、IL-4、IL-5和sCD14的水平，以阐明这些指标在AD、湿疹和荨麻疹患者中的临床意义和相互关系。ECP水平仅在AD患者中升高，而sE-选择素水平不仅在AD患者中升高，而且在非特应性湿疹患者中也呈严重程度依赖性升高。治疗后两种标志物水平均明显下降。ECP水平与嗜酸性粒细胞数量、sE-选择素水平与瘙痒评分、sE-选择素水平与IgE水平之间存在显著的相关性。我们还观察了CC趋化因子受体之一CCR3在培养的角质形成细胞以及正常皮肤和炎症皮肤中的表达。CCR3作为Th2标志物备受关注。角质形成细胞确实在蛋白和信使核糖核酸水平表达CCR3，并且这种表达被炎症所增强。我们现在正在研究角质形成细胞对CCR3表达的调节机制。皮肤树突状细胞免疫组织化学未检测到CCR3的表达。

We have already examined 1) the serum levels of IL-4 and IL-5,2) intracellular cytokine profiles of peripheral blood mononuclear cells, and 3) chronological changes of serum markers of outgrown patients, in atopic dermatitis (AD). We have found 1) that serum levels of IL-4 and IL-5 are not useful markers for AD,2) that the flow cytometric analysis of mononuclear cells discloses a Th2-dominant pattern in AD,and 3) that serum markers such as ECP and sELAM-1 rapidly decrease in outgrown AD patients. In 1997 projects we further investigated the serum levels of ECP,sELAM-1, IL-4, IL-5 and sCD14 in order to elucidate the clinical and mutual relevance of these markers in AD,eczema and urticaria patients. The levels of ECP are elevated only in the AD patients, whereas the sE-selectin levels are higher not only in AD but also in non-atopic eczema in a severity-dependent manner. The levels of both markers significantly diminish after the treatment. Significant correlation exists between ECP levels and number of eosinophils, sE-selectin levels and itch scores, and sE-selectin levels and IgE levels. No significant changes are observed in the sCD14 and IL-4 levels (submitted for publication).We also invetigated the expression of CCR3, one of the receptors for CC chemokines, in cultured keratinocytes as well as normal and inflammatory skins in situ. CCR3 is recentry paid attention as a Th2 marker. Keratinocytes indeed express CCR3 in a protein and mRNA level and the expression is augmented by inflammation. We are now examining the regulatory mechanism of CCR3 expression by keratinocytes. The expression of CCR3 is not detected by cutaneous dendritic cells immunohistologically.