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.

白介素（IL）-18是促炎细胞因子，现在被认为是两个辅助T细胞（TH）1和2细胞因子产生的重要调节剂。进行这项研究是为了确定IL-18是否参与儿童难治性特应性皮炎（AD）的病原体。外周血单调细胞（PBMC）是从没有任何过敏性疾病的儿童和对照儿童的儿童那里获得的，然后用脂多糖（LPS）或植物羟藻戊丁素（PHA）培养。 AD儿童中的IL-18分泌（几何平均值（GM）= 172 pg/ml）明显高于非过敏儿童（118 pg/ml）。相反，AD儿童中的干扰素 - γ（IFN-γ）分泌（GM = 6.8 IU/mL）显着低于非过敏对照（GM = 20.7 IU/mL）的分泌。由于已知IL-18与IL-12和IL-2协同诱导IFN-γ合成，因此研究了通过PBMC组合IL-18和IL-12或IL-2对IFN-γ产生的诱导效应。在由IL-18+IL-12刺激的20种非过敏对照的所有PBMC中检测到IFN-γ的产生，但是，21个AD儿童中有5个儿童中有5个的结果在IFN-γ产生的检测极限下。与IL-2合作，IL-18可能会诱导所有非过敏儿童的PBMC和21个AD儿童中的20个PBMC产生IFN-γ，这表明IL-12信号级联的损害大约在四分之一的AD儿童中涉及。因此，用流式细胞仪分析了CD4+ T细胞的IL-12受体表达。在T4+细胞上IL-12β-β-1受体表达中，AD儿童（6.5±1.9％）（6.5±1.9％）和非过敏儿童（6.1±1.1％）之间的结果在统计学上没有差异。不幸的是，CD4+ T细胞上IL-12β-2受体表达的测量尚未成功。