title: Elevated serum and synovial fluid levels of interleukin-37 in patients with rheumatoid arthritis: Attenuated the production of inflammatory cytokines.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  An 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  IL-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.
authors.affiliation: Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang 110001, China. Electronic address: xialipingcmu@163.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism*
chemical_list: D016207:Cytokines; C508587:IL37 protein, human; D018836:Inflammation Mediators; D007375:Interleukin-1
keywords: Interleukin-17; Interleukin-37; Interleukin-6; Rheumatoid arthritis