title: Increased expression of IL-37 in patients with Graves' disease and its contribution to suppression of proinflammatory cytokines production in peripheral blood mononuclear cells.
abstract: BACKGROUND
  Interleukin-37 (IL-37), a member of IL-1 family, is primarily an anti-inflammatory cytokine, which reduces systemic and local inflammation. However, the expression and role of IL-37 in Graves' disease (GD) remains unknown. This study aims to measure the levels of serum and peripheral blood mononuclear cells (PBMCs) IL-37 in patients with Graves' disease and to examine its association with disease activity. Furthermore, we investigate the effect of IL-37 on proinflammatory cytokines involved in the pathogenesis of GD.
  
  
  METHODS
  The expressions of IL-37, TNF-α, IL-6, and IL-17 mRNA in peripheral blood mononuclear cells (PBMCs) of 40 patients with Graves' disease were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the levels of IL-37, TNF-α, IL-6, and IL-17 in serum were detected by enzyme-linked immunoassay (ELISA). The correlation of serum IL-37 levels with cytokines and disease activity in Graves' disease patients were investigated. The expressions of cytokines TNF-α, IL-6, and IL-17 in PBMCs under recombinant IL-37 stimulation were determined by RT-PCR and ELISA respectively.
  
  
  RESULTS
  The levels of IL-37, TNF-α, IL-6, and IL-17 in PBMCs and serum were significantly increased in patients with GD compared with healthy controls (HC). Serum IL-37 were closely correlated with TNF-α, IL-6, IL-17, thyrotropin (TSH), free thyroxine (FT4),free triiodothyronine (FT3) and thyrotropin receptor antibody (TRAB). GD patients with active disease showed higher IL-37 mRNA and serum protein levels compared with those with inactive disease as well as HC. Moreover, IL-37 suppressed the production of IL-6, IL-17 and TNF-α in PBMCs of patients with GD.
  
  
  CONCLUSIONS
  Increased level of IL-37 in patients with GD are associated with TNF-α, IL-6, IL-17 and disease activity, and it plays a protective role against inflammatory effect in GD by inhibiting the production of proinflammatory cytokines. Thus, IL-37 may provide a novel research target for the pathogenesis and therapy of GD.
authors.affiliation: Biological therapy institute, Shenzhen University School of Medicine, Shenzhen, China; Department of Pathogen biology and immunology, Shenzhen University School of Medicine, Shenzhen, China; Shenzhen City Shenzhen University Immunodiagnostic Technology Platforms, Shenzhen, China.
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Biological therapy institute, Shenzhen University School of Medicine, Shenzhen, China; Department of Pathogen biology and immunology, Shenzhen University School of Medicine, Shenzhen, China; Shenzhen City Shenzhen University Immunodiagnostic Technology Platforms, Shenzhen, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Biological therapy institute, Shenzhen University School of Medicine, Shenzhen, China; Department of Pathogen biology and immunology, Shenzhen University School of Medicine, Shenzhen, China; Shenzhen City Shenzhen University Immunodiagnostic Technology Platforms, Shenzhen, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Biological therapy institute, Shenzhen University School of Medicine, Shenzhen, China; Department of Pathogen biology and immunology, Shenzhen University School of Medicine, Shenzhen, China; Shenzhen City Shenzhen University Immunodiagnostic Technology Platforms, Shenzhen, China.
authors.forename: Bingni
authors.initials: B
authors.lastname: Chen
authors.affiliation: Biological therapy institute, Shenzhen University School of Medicine, Shenzhen, China; Department of Pathogen biology and immunology, Shenzhen University School of Medicine, Shenzhen, China; Shenzhen City Shenzhen University Immunodiagnostic Technology Platforms, Shenzhen, China.
authors.forename: Jinshun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Biological therapy institute, Shenzhen University School of Medicine, Shenzhen, China; Department of Pathogen biology and immunology, Shenzhen University School of Medicine, Shenzhen, China; Shenzhen City Shenzhen University Immunodiagnostic Technology Platforms, Shenzhen, China.
authors.forename: Kunzhao
authors.initials: K
authors.lastname: Huang
authors.affiliation: Biological therapy institute, Shenzhen University School of Medicine, Shenzhen, China; Department of Pathogen biology and immunology, Shenzhen University School of Medicine, Shenzhen, China; Shenzhen City Shenzhen University Immunodiagnostic Technology Platforms, Shenzhen, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006111:Graves Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; C508587:IL37 protein, human; D018836:Inflammation Mediators; D007375:Interleukin-1; D012333:RNA, Messenger