ABSTRACT
Interleukin-18 binding protein [IL-18BP] is functioning as a natural anti-inflammatory and immunosuppressive molecule by neutralizing the effects of IL-18 during inflammation. This study aimed to identify the role of IL-18BPa in the regulation of immune responses associated with the pathogenesis of RA. 65 RA patients, 22 OA patients, and 40 sex and age matched healthy donors were enrolled in this study. Synovial specimens were obtained through synovectomy or arthroscopic procedures. SFMC and PBMC were prepared by using Ficoll-Hypaque separation procedure. Superarray analysis was used to measure the expression profile of immune-related genes in normal PBMC treated with recombinant human IL-18BPa. The mRNA levels of Th1 and Th2 cytokines were measured by Real-time PCR, and the protein levels of IFN-gamma, IL-4 were detected by ELISA. SuperArray analysis of immune related gene expression profile in normal PBMC treated with IL-18BPa indicated decreases in the gene expression of IFN- gamma and its regulatory molecules STAT-1 and STAT-2. This study pointed out that IL-18BPa has additional anti-inflammatory property through downregulating the expression of IFN- gamma and IL-12, at the same time, upregulating the expression of IL-4 and IL-10. Both IFN- gamma and IL-12 could upregulate the mRNA and protein levels of IL-18BPa in both the normal and RA subjects. Our results demonstrated the importance of IL-18BPa as an immune regulatory molecule and as a promising therapy for treating RA