Abstract
Objectives: 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.
Materials and Methods: 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.
Results: 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 upregulated the mRNA and protein levels of IL-18BPa in both the normal and RA subjects.
Conclusion: Our results demonstrated the importance of IL-18BPa as an immune regulatory molecule and as a promising therapy for treating RA.