Background/Purpose: Interleukin-37 (IL-37) is one of few anti-inflammatory cytokines belonging to the IL-1 cytokine family. It is mainly produced by immune cells of innate immunity such as monocytes and dendritic cells. Recent data suggest its role in several autoimmune and cardiovascular diseases. The aim of this study was to analyse the expression of IL-37 in synovial tissue, synovial fluid (SF) and serum of patient with established rheumatoid arthritis (RA) and osteoarthritis (OA) and to analyse its potential role in the pathogenesis of RA.

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. All RA patients fulfilled the 2010 ACR/EULAR criteria for RA. Disease activity was assessed based on the Disease Activity Score of 28 joints (DAS28-ESR). For in vitro studies, fibroblast-like synoviocyte (FLS) 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 localize IL-37 protein expression in synovial tissue cells (n=4-6) and FLS.

Results: The expression of IL-37 was upregulated in synovial tissue of patients with RA compared to OA, and co-localized with B-lymphocyte, T-lymphocyte, fibroblast-like synoviocyte (FLS) and macrophage specific markers. Further, stimulation with lipopolysacharide (LPS) increased the nuclear expression of IL-37 in synovial fibroblasts cell cultures. 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 the serum levels, of IL-37 were significantly higher in RA patients compared to OA patients (77.50 ± 56.73 vs. 57.00 ± 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 a leukocytes count in SF (r=0.33, p<0.05) and serum levels of CRP (r=0.31, p<0.05). Interestingly, serum levels of IL-37 negatively correlated with high density lipoprotein (HDL) levels (r=-0.33, p<0.05) and positively with atherogenic index (r=0.34, p<0.05), but not with low density lipoprotein (LDL)-cholesterol, triacylglycerol (TAG) or total cholesterol levels.

Conclusion: Our data suggest possible role of IL-37 in accelerated atherosclerosis and increased cardiovascular burden in patients with RA.

Acknowledgement: This study was supported by Research Project No. 00023728.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-37-is-associated-with-increased-atherogenesis-in-patients-with-rheumatoid-arthritis/