Decreased Interleukin-37 Expression in Vogt-Koyanagi-Harada Disease and Upregulation Following Immunosuppressive Treatment

Zi Ye, Chaokui Wang, Jihong Tang, Yan Zhou, Lin Bai, Yunjia Liu, Aize Kijlstra, Peizeng Yang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Web of Science)

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-kappa B) activation were measured by flow cytometry. VKH patients showed a decreased IL-37 and IL-27 expression and increased IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) levels in PBMC culture supernatants. IL-37 significantly inhibited the production of IL-1 beta, IL-6, and TNF-alpha, 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-gamma), 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.
Original languageEnglish
Pages (from-to)265-272
JournalJournal of Interferon and Cytokine Research
Volume35
Issue number4
DOIs
Publication statusPublished - 1 Apr 2015

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