STUDIES OF IL-18 IN CHILDREN WITH REFRACTORY ATOPIC DERMATITIS

白介素18(IL-18)是一种促炎细胞因子，目前被认为是辅助性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是否参与儿童难治性特应性皮炎(AD)的发病机制。采集难治性AD患儿和正常对照组儿童外周血单个核细胞(PBMC)，加入脂多糖(LPS)或植物血凝素(PHA)进行体外培养。AD患儿IL-18分泌量几何均数(Gm)为172pg/ml，明显高于非变态反应组(118pg/ml)。而阿尔茨海默病儿童干扰素-γ的分泌量(Gm=6.8IU/ml)明显低于非过敏对照组(Gm=20.7IU/ml)。鉴于IL-18与IL-12和IL-2协同诱导干扰素-γ的合成，我们在体外观察了IL-18和IL-12或IL-2联合应用对PBMC产生干扰素-γ的诱导作用。在IL-18+IL-12刺激下，20例非变态反应对照的PBMC均可检测到干扰素-γ的产生，而21例AD患儿中有5例的PBMC均未检测到干扰素-γ的产生。在IL-2的协同作用下，IL-18能够诱导所有非过敏儿童和21名AD儿童中的20名儿童的PBMC产生干扰素-γ，这表明大约四分之一的AD儿童参与了IL-12信号级联的损害。为此，用流式细胞仪分析了CD4+T细胞IL-12受体的表达。AD患儿T4+细胞IL-12β-1受体表达(6.5±1.9%)与非过敏患儿(6.1±1.1%)比较差异无统计学意义。遗憾的是，对β+T细胞表面IL-12 CD4-2受体表达的检测尚未成功。

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.