Khalid KE, Gue TB, Sun W, Nie H, Liu A, Mohamed E M Ahmed, Saeed OK and Zhang JZ
Objective: This study aimed to identify the role of IL-18BPa in the regulation of immune responses associated with the pathogenesis of Rheumatoid Arthritis.
Methods: 65 Rheumatoid Arthritis (RA) patients, 22 Osteoarthritis (OA) patients, and 40 sex and age matched healthy donors were enrolled in this study. Synovial fluids mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) were prepared by using Ficoll-Hypaque separation procedure. Super Array analysis was used to measure the expression profile of immune-related genes in RA synovial tissues (RA-ST) and in normal PBMC treated with recombinant human IL-18 binding protein a (IL-18BPa). The mRNA levels of T-helper 1 (TH1) and T-helper 2 (TH2) cytokines were measured by real-time PCR, and the protein levels of IFN-γ, IL-4 and IL-18BPa autoantibodies were detected by ELISA.
Results: High expression of IL-18BPa protein and messenger RNA (mRNA) are found in RA-SF and RA-ST. SuperArray analysis of immune related gene expression profile in normal PBMC treated with IL-18BPa indicated decreases in the gene expression of IFN-γ. IL-18BPa downregulated the mRNA expression of IFN-γ and IL-12, as well as, upregulated the mRNA expression of IL-4 and IL-10 in RA and normal subjects. IFN-γ and IL-12 upregulated the mRNA and protein expression of IL-18BPa in RA subjects. Autoantibodies against IL-18BPa were detected in plasma of RA patients (41.7%), in healthy subjects (4.0%), and none of OA patients, and also detected in SF of RA patients (37.9%) and OA patients (9%).
Conclusion: This study emphasizes the anti-inflammatory properties of IL-18BPa on cytokines milieu and the IL-18BPa auto-antibodies may play a role in aberrant regulation of IL-18BPa in RA patients.