Elevated serum and synovial fluid levels of interleukin-37 in patients with rheumatoid arthritis: Attenuated the production of inflammatory cytokines

• IL-37 act as an anti-inflammatory cytokine in RA progression.
• The plasma and SF levels of IL-37 were significantly increased in RA patients.
• The levels of IL-37 in plasma and SF decreased following TNF-a blockade therapy.
• IL-37 can suppress the expressions of pro-inflammatory cytokines.
• Adding IL-37 may be a novel therapy for RA.

ObjectivesTo measure the serum and synovial fluid (SF) levels of interleukin (IL)-37 in patients with rheumatoid arthritis (RA) and to investigate the effect of recombinant human (rh)IL-37 on inflammatory cytokine production (tumor necrosis factor [TNF]-α, IL-6, IL-17 and IL-10) by peripheral blood mononuclear cells (PBMCs) in RA patients.MethodsAn enzyme-linked immunosorbent assay (ELISA) was used to analyse the serum and SF IL-37 levels. RhIL-37 was used to stimulate RA patient PBMCs. The supernatant TNF-α, IL-17, IL-6 and IL-10 levels were detected with ELISAs.ResultsThe serum IL-37 levels in RA patients were significantly increased compared with those of osteoarthritis (OA) and healthy controls (HC), and they were especially elevated in RA patients with positive rheumatoid factor (RF) and anti-citrullinated peptide antibody (CCP) levels. Furthermore, the serum IL-37 levels were positively correlated with RF values. In 20 matched RA SF and serum samples, the SF IL-37 levels were much higher than those in the serum. After anti-TNF-α therapy, the serum IL-37 levels significantly decreased. Additionally, rhIL-37 significantly down-regulated TNF-α, IL-17 and IL-6 production by RA patient PBMCs.ConclusionsIL-37 is an important anti-inflammatory cytokine in the control of RA pathogenesis by suppressing inflammatory cytokine production. Thus, IL-37 administration may be a novel therapy for RA.