Interleukin-18 enhances the production of interleukin-8 by eosinophils

Interleukin-18 (IL-18), a proinflammatory cytokine, leads to IFN-gamma prod uction by NK or T cells, induces Th1 differentiation and suppresses IgE syn thesis by B cells when acting on responding cells together with IL-12. IL-1 8 also exhibits biological activities related to allergic inflammation such as histamine or IL-4 release from basophils and accumulation of eosinophil s in localized lesions in allergic model mice. In this study, Reverse trans cription (RT)-PCR analysis revealed that IL-18 receptor alpha chain mRNA wa s expressed in both freshly prepared eosinophils and two eosinophilic cell lines (YY-1 and EoL-1 cells). Flow cytometry and RT-PCR analyses revealed t hat the treatment of YY-1 cells with n-butyric acid promoted cell maturatio n and caused an enhancement of IL-18 receptor alpha chain expression. IL-18 had little effect on the survival of peripheral eosinophils, but it dose-d ependently augmented IL-8 synthesis by YY-I cells. In addition, IL-18-media ted up-regulation of IL-8 expression in eosinophils from a patient sufferin g from hyper-eosinophilic syndrome was confirmed. Our findings using periph eral blood eosinophils and eosinophilic cell line suggest the functional im portance of IL-18 in the induction of IL-8 and a potential proinflammatory role in allergy.