Interleukin-37 expression is decreased in Behçet's disease and is associated with inflammation

Immunol Lett. 2015 Oct;167(2):87-94. doi: 10.1016/j.imlet.2015.08.001. Epub 2015 Aug 4.

Abstract

Interleukin-37 (IL-37) exerts broad inhibitory properties on the innate inflammatory and acquired immune responses. This study was set up to investigate the expression of IL-37 in Behçet disease (BD) and to explore its possible regulatory role during inflammation. IL-37 protein levels and mRNA expression in lipopolysaccharides (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) from 50 BD (30 patients in active stage) patients and 20 healthy controls were assayed by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Cytokines in the serum and the supernatants of stimulated PBMCs and CD4(+) T cells were assayed by ELISA. Active BD patients showed a decreased IL-37 expression and increased IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels in serum and in PBMC culture supernatants. Active BD patients treated with corticosteroids showed an enhanced IL-37 production. Recombinant IL-37 (rIL-37) induced a significant decrease of inflammatory cytokines (IL-1β, IL-6, and TNF-α). It also markedly decreased IL-17 expression in PBMCs and CD4(+) T cells from active BD patients. The present study suggests that a decreased IL-37 expression in BD patients is associated with an increased inflammatory response. Corticosteroid treatment of active BD patients is associated with an increased expression of IL-37 mRNA, which suggests that treatment may partly exert its immunosuppressive effect by regulating IL-37 production and reducing inflammatory cytokines.

Keywords: Behçet disease; IL-17; IL-1β; IL-6; Interleukin-37; TNF-α.

MeSH terms

  • Adult
  • Behcet Syndrome / diagnosis
  • Behcet Syndrome / drug therapy
  • Behcet Syndrome / genetics*
  • Behcet Syndrome / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation*
  • Humans
  • Inflammation / genetics*
  • Inflammation / immunology
  • Inflammation Mediators / metabolism
  • Interleukin-1 / genetics*
  • Interleukin-1 / metabolism
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Cytokines
  • IL37 protein, human
  • Inflammation Mediators
  • Interleukin-1
  • RNA, Messenger