title: Decreased interleukin-37 expression in Vogt-Koyanagi-Harada disease and upregulation following immunosuppressive treatment.
abstract: Interleukin-37 (IL-37) is emerging as an important inhibitor of immune response. This study was set up to investigate the expression of IL-37 in Vogt-Koyanagi-Harada (VKH) disease and to explore its possible regulatory role during inflammation. Twenty-four untreated active VKH patients, 10 VKH patients receiving corticosteroids and cyclosporin A (CsA), and 35 healthy controls were included in this study. IL-37 expression in lipopolysaccharides (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) from these 3 groups was assayed by real-time polymerase chain reaction (RT-PCR) and flow cytometry. Cytokines in the supernatants of stimulated PBMCs and CD4(+) T cells were assayed by enzyme-linked immunosorbent assay (ELISA). Mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation were measured by flow cytometry. VKH patients showed a decreased IL-37 and IL-27 expression and increased IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels in PBMC culture supernatants. IL-37 significantly inhibited the production of IL-1β, IL-6, and TNF-α, but induced IL-27 expression. VKH patients treated with corticosteroids combined with CsA showed a regression of the intraocular inflammation, and treatment was associated with an enhanced IL-37 production. IL-37 did not affect the production of IL-17, interferon-gamma (IFN-γ), or IL-10 from CD4(+) T cells. The present study suggests that a decreased IL-37 expression in VKH patients is associated with a reduced control of the inflammatory response. Treatment of VKH patients with corticosteroids and CsA is associated with an increased expression of IL-37, which suggests that corticosteroids and CsA may partly exert their immunosuppressive effect by upregulating IL-37 production.
authors.affiliation: 1 The First Affiliated Hospital of Chongqing Medical University , Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, People's Republic of China .
authors.forename: Zi
authors.initials: Z
authors.lastname: Ye
authors.forename: Chaokui
authors.initials: C
authors.lastname: Wang
authors.forename: Jihong
authors.initials: J
authors.lastname: Tang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Lin
authors.initials: L
authors.lastname: Bai
authors.forename: Yunjia
authors.initials: Y
authors.lastname: Liu
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014607:Uveomeningoencephalitic Syndrome / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; C508587:IL37 protein, human; D007166:Immunosuppressive Agents; D007375:Interleukin-1