STUDIES OF IL-18 IN CHILDREN WITH REFRACTORY ATOPIC DERMATITIS

白细胞介素（IL）-18是一种促炎细胞因子，现在被认为是辅助性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。取难治性AD患儿和无变态反应性疾病的对照组儿童外周血单个核细胞（PBMC），分别用脂多糖（LPS）和植物血凝素（PHA）培养。AD患儿IL-18分泌量（几何平均值（gm）=172 pg/ml）显著高于非过敏儿童（118 pg/ml）。AD患儿IFN-γ分泌量（gm=6.8 IU/ml）明显低于正常对照组（gm=20.7 IU/ml），IL-18与IL-12、IL-2协同诱导IFN-γ合成，本研究探讨IL-18与IL-12或IL-2联合对PBMC产生IFN-γ的体外诱导作用。20名非过敏对照者经IL-18+IL-12刺激后，所有PBMC均检测到IFN-γ产生，但21名AD儿童中有5名的结果低于IFN-γ产生的检测限。与IL-2协同作用，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IFN-γ，这表明大约四分之一的AD儿童参与了IL-12信号级联的损伤。为此，用流式细胞术分析CD 4 + T细胞的IL-12受体表达。AD患儿T4+细胞IL-12 β-1受体表达（6.5±1.9%）与非过敏儿童（6.1±1.1%）比较差异无统计学意义。遗憾的是，对CD 4 + T细胞上IL-12 β-2受体表达的测量尚未成功。

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.