Role Of IL-18 In Atopic Asthma Is Determined By Balance Of LL-18/IL-18BP/IL-18R

ObjectiveThe current study is to investigate the expression of IL-18/IL-18R/IL-18 BP in asthmatics and ovalbumin(OVA)-sensitized mice,and elucidate the relationship among IL-18/IL-18R/IL-18 BP in asthma.MethodsLevels of IL-18 and IL-18 BP in plasma of healthy controls and asthmatics were determined by ELISA.Expression of IL-18,IL-18 BP and IL-18 R in monocytes and neutrophils of asthmatics and OVA-sensitized mice were analyzed by flow cytometry.ResultsIt was found that plasma levels of IL-18 and IL-18 BP were elevated in asthma.The ratio between plasma concentrations of IL-18 and IL-18 BP was 1:12.8 in asthmatic patients.We demonstrated that 13-fold more monocytes,17.5-fold more neutrophils and 4.1-fold more B cells express IL-18 BP than IL-18 in asthmatic blood,suggesting that there is excessive amount of IL-18 BP to abolish actions of IL-18 in asthma.We also discovered that more IL-18R+ monocytes,neutrophils and B cells are located in asthmatic blood.Once injected,IL-18 eliminated IL-18R+ monocytes in blood,but upregulated expression of IL-18 R in lung macrophages of OVA-sensitized mice.ConclusionsRole of IL-18 in asthma is very likely to be determined by balance of IL-18/IL-18BP/IL-18 R expression in inflammatory cells.Therefore,IL-18 R blocking or IL-18 BP activity enhancing therapies may be useful for treatment of asthma.