IL-18 receptor antagonist in the pathogenesis and treatment of inflammatory respiratory disease

与野生型Balb/c小鼠相比，卵蛋白致敏和攻击肺特异性IL-18转基因小鼠的气道高反应性和伴随有CD4+T细胞、CD8+T细胞、嗜酸性粒细胞、中性粒细胞和巨噬细胞的气道炎症细胞显著增加。过敏性哮喘患者血清中可溶性IL-18受体复合体(sIL-18R)水平的变化与哮喘患者肺组织中IL-18蛋白的过度表达可诱导1、2型细胞因子和呼吸道炎症反应，导致哮喘患者的气道高反应性增加有关。我们获得了年龄匹配的19例过敏性哮喘患者、14例过敏性非哮喘患者和14例健康对照的血清。过敏性哮喘患者血清sIL-18R水平(32.9±4.3 ng/ml)显著高于非过敏性哮喘患者(18.8±1.5 ng/ml)和健康对照组(16.1±1.6 ng/ml)。在整个人群中，血清sIL-18R水平与IgE水平显著相关。因此，sIL-18R可能在过敏性哮喘的炎症过程中起重要作用。

Airway hyperresponsiveness and airway inflammatory cells accompanied with CD4+ T cells, CD8+ T cells, eosinophils, neutrophils, and macrophages were significantly increased in ovalbumin-sensitized and challenged lung-specific IL-18 transgenic mice, as compared to wild type Balb/c mice. Overexpressing the IL-18 protein in the lungs induces type 1 and type 2 cytokines and airway inflammation, and results in increasing airway hyperresponsiveness via CD4+ T cells and IL-13 in asthma.We measured serum levels of soluble IL-18 receptor complex (sIL-18R) in patients with allergic asthma. We obtained sera from age-matched 19 allergic asthmatic subjects, 14allergic non-asthmatic subjects, and 14 healthy controls. The serum levels of sIL-18R in allergic asthmatics (32.9±4.3 ng/ml) were significantly higher than those in non-asthmatic allergic subjects (18.8±1.5 ng/ml) and healthy controls (16.1±1.6 ng/ml). In the entire population, there was a significant correlation between serum sIL-18R evels and the levels of IgE. Therefore, sIL-18R may play an important role in the inflammatory process of allergic asthma.