STUDIES OF IL-18 IN CHILDREN WITH REFRACTORY ATOPIC DERMATITIS

IL-18 在难治性特应性皮炎儿童中的研究

基本信息

批准号：
13670818
负责人：
MATSUMOTO Tomoaki
金额：
$ 1.73万
依托单位：
KUMAMOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2004
项目状态：
已结题

项目摘要

Interleukin(IL)-18 is a proinflammatory cytokine and is now recognized an important regulator of both helper T cells(Th) 1 and 2 cytokine production. This study was performed to determine whether or not IL-18 is involved in the pathogeneses of refractory atopic dermatitis(AD) in childhood. Peripheral blood mononudear cells(PBMC) were obtained from children with refractory AD and control children who did not have any allergic disease, and then cultured with lipopolysaccharide(LPS) or phytohaemagglutinin(PHA). IL-18 secretion in the AD children(geometric mean (gm)=172 pg/ml) was significantly higher than that in non-allergic children(118 pg/ml). In contrast, interferon-gamma(IFN-γ) secretion in the AD children(gm=6.8 IU/ml) was significantly lower than that in non-allergic controls(gm=20.7 IU/ml).Since IL-18 has been known to synergize with IL-12 and IL-2 to induce IFN-γ synthesis, the inducing effect in vitro of combining IL-18 and IL-12 or IL-2 on IFN-γ production by PBMC was investigated. IFN-γ production was detected in all PBMCs from 20 non-allergic controls stimulated with IL-18+IL-12, however, the results for five of 21 AD children were under the detection limit for IFN-γ production. In collaboration with IL-2, IL-18 was able to induce IFN-γ production by PBMCs from all non-allergic children and 20 of 21 AD children, suggesting that impairment of the IL-12 signal cascade was involved in around a quarter of the AD children. For this reason, the CD4+ T cells were analyzed for IL-12 receptor expression with flow cytometry. The results were not statistically different between the AD children(6.5±1.9%) and the non-allergic children (6.1±1.1%) in IL-12 β-1 receptor expression on the T4+ cells. Unfortunately, the measurement for IL-12 β-2 receptor expression on CD4+ T cells has not been succeeded.

白细胞介素 (IL)-18 是一种促炎细胞因子，现已被认为是辅助 T 细胞 (Th) 1 和 2 细胞因子产生的重要调节因子。本研究旨在确定 IL-18 是否参与难治性的发病机制。儿童期特应性皮炎（AD）从难治性AD儿童和没有任何过敏性疾病的对照儿童中获取外周血单核细胞（PBMC），然后进行培养。 AD儿童的脂多糖(LPS)或植物血凝素(PHA)分泌量(几何平均值(gm)=172 pg/ml)显着高于非过敏儿童(118 pg/ml)。 AD儿童干扰素γ(IFN-γ)分泌量(gm=6.8 IU/ml)明显低于正常儿童非过敏对照(gm=20.7 IU/ml)。由于已知IL-18与IL-12和IL-2协同诱导IFN-γ合成，因此IL-18和IL-1组合的体外诱导效果研究了 12 或 IL-2 对 PBMC 产生 IFN-γ 的影响，在 20 个非过敏对照刺激的所有 PBMC 中检测到了 IFN-γ 产生。然而，IL-18+IL-12 21 名 AD 儿童中有 5 名的结果低于 IFN-γ 产生的检测限。通过与 IL-2 合作，IL-18 能够诱导来自 PBMC 的 IFN-γ 产生。所有非过敏儿童和 21 名 AD 儿童中的 20 名，表明大约四分之一的 AD 儿童涉及 IL-12 信号级联损伤。因此，对 CD4+ T 细胞进行了分析。流式细胞术检测AD儿童(6.5±1.9%)与非过敏儿童(6.1±1.1%)T4+细胞上IL-12β-1受体表达差异无统计学意义。不幸的是，CD4+T细胞上IL-12β-2受体表达的测量尚未成功。