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

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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.