Expression of interleukin-18, IL-18BP, and IL-18R in serum, synovial fluid, and synovial tissue in patients with rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic immunological disease, the invasive monocytes/macrophages and lymphocytes present in synovial cells and synovial tissue produce many cytokines and inflammatory mediators by paracrine signaling and plays a role in the pathological progress in RA patients. Interleukin-18 (IL-18) is a representative proinflammatory factor and displays multiple biological functions. This study was designed to investigate the expression of IL-18 and its receptor (IL-18R) and IL-18 binding protein (IL-18BP) in serum, synovial fluid, and synovial tissue of patients with RA, and to identify the pathological role of IL-18 in RA. Serum, synovial fluid, and synovial tissue were obtained from RA patients. Samples from patients with osteoarthritis and healthy people were obtained as controls. Levels of IL-18, IL-18BP, and PGE2 in serum and synovial fluid were measured by enzyme-linked immunosorbent assay. The biological activity of IL-18 in serum and synovial fluid was detected on the basis of IFN-gamma secretion from IL-18-responding human myelomonocytic KG-1 cells. NO in serum and synovial fluid was detected by Griess reaction. Expression of IL-18, IL-18BP, IL-18R, iNOS, and COX-2 mRNA and protein in synovial tissues was determined by quantitative reverse transcriptase polymerase chain reaction and Western blot. This study shows the expression levels of IL-18, IL-18R, iNOS, COX-2, and the biological activity of IL-18 in both serum and synovial fluid and tissue of patients with RA were significantly increased compared with the corresponding samples from the two control groups. In addition, expression of IL-18BP in patients with RA was decreased compared with samples from the two control groups. In conclusion, the overexpression of IL-18 and IL-18R may play an important role in the pathogenesis of RA.

Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation

“…This response to uric acid has recently been further elucidated as being the result of activation of the NALP3 inflammasome with subsequent production of the active forms of IL-18 and IL-1β (5). The mean concentration of IL-18 we measured in synovial fluid was 1.4 times higher than previously reported for OA synovial fluid, 3.5 times higher than previously reported for normal synovial fluid, but still 2 to 3 times lower than typically seen in rheumatoid arthritis (RA) (18,19). IL-1β is not typically detected in normal synovial fluid (20,21) and is very low (3.91 ± 4.66 pg/mL) or undetectable (22) in OA synovial fluid.…”

Comparative genome-wide gene expression analysis of rheumatoid arthritis and osteoarthritis

“…RA is a chronic immunological disease in which invasive monocytes and lymphocytes in synovial cells and synovial tissue produce numerous cytokines and inflammatory mediators of paracrine signaling that play a role in the pathological progress in RA patients. The overexpression of IL-18 and IL-18R may be important in the pathogenesis of RA (Shao et al, 2009). Most interleukins, including IL-1R1, IL-1R2, and IL-8, were identified in both RA-and OA-associated pathways, including MAPK signaling and Tolllike receptor signaling.…”

Honokiol: an effective inhibitor of tumor necrosis factor-α-induced up-regulation of inflammatory cytokine and chemokine production in human synovial fibroblasts

“…Activation of NFkB plays a central role in inflammation. It not only up-regulates the expression of genes encoding COX-2 and iNOS in RASFs [1], but also induces their products (PGE2 and NO), which are overexpressed in the articular synovial tissues of RA patients [20]. The corresponding pathways are activated through appropriate extracellular stimulation, such as stress or pro-inflammatory cytokines including lipopolysaccharide and TNF-a [21].…”