Background Interleukin-37 (IL-37) is one of few anti-inflammatory cytokines produced mainly by monocytes and dendritic cells. Recent data suggest its role in several autoimmune diseases. The aim of this study was to analyse the expression of IL-37 in synovial tissue, synovial fluid and serum of patient with established rheumatoid arthritis (RA) and osteoarthritis (OA) and to analyse its potential role in RA.
Materials and methods Serum and synovial fluid levels of IL-37 were determined in 52 patients with established RA and 49 control subjects with osteoarthritis (OA) by ELISA. Disease activity was assessed based on the Disease Activity Score of 28 joints (DAS28-ESR). For in vitro studies, synovial tissue fibroblasts (SFs) were obtained from patients with RA and OA (n=6–9). Serum C-reactive protein (CRP) and lipid profile were determined. Immunofluorescence and immunohistological staining was used to detect IL-37 protein expression in synovial tissue (n=4–6) and SFs.
Results The expression of IL-37 was upregulated in synovial tissue of patients with RA compared to OA, and co-localised with B-cell, T-cells, SFs and macrophages. In addition, stimulation with LPS increased the expression of IL-37 in RA synovial fibroblasts. However, the serum levels of IL-37 were significantly higher compared to synovial fluid levels of RA and OA patients (77.50±56.73 vs. 51.50±43.17, p<0.001; 57.00±73.25 vs. 27.00±38.38, p<0.001, respectively). Further, the synovial fluid levels, but not serum levels of IL-37 were significantly higher in RA patients compared to OA patients (77.5±56.73 vs. 57.0±73.25, p<0.01) and there was a significant correlation between serum and synovial fluid IL-37 levels in RA patients (r=0.55, p<0.001). Although, neither serum nor synovial fluid IL-37 levels were associated with disease activity, synovial fluid IL-37 levels positively correlated with serum levels of CRP (r=0.31, p<0.05). Interestingly, serum levels of IL-37 negatively correlated with high density lipoprotein levels (r=−0.328, p<0.05) and positively with atherogenic index (r=0.34, p<0.05), suggesting that IL-37 can contribute to the cardiovascular manifestations in RA.
Conclusions Our data suggest possible role of IL-37 in accelerated atherosclerosis and increased cardiovascular burden in patients with RA.
Acknowledgement Supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organisation 00023728 (Institute of Rheumatology).