Elevated Interleukin 37 Expression Associated With Disease Activity in HLA-B27 Associated Anterior Uveitis and Idiopathic Anterior Uveitis

Background & Objective: Interleukin 37 (IL-37) is an important regulator of the anti-inflammatory T-cell response. In this study, we investigated its expression and function in peripheral blood mononuclear cells (PBMCs) of patients with HLA-B27 associated acute anterior uveitis (AAU) and idiopathic AAU. Methods: 15 patients with HLA-B27-associated AAU, 10 patients with idiopathic AAU and 22 controls were recruited to this study from August 2013 to December 2016. Complete ophthalmological examinations were performed and clinical features were clearly documented. Blood samples were collected and peripheral blood mononuclear cells were extracted. IL-37 messenger RNA (mRNA) and protein expression in peripheral blood mononuclear cells (PBMCs) were examined by performing RT-PCRs and western blot, respectively. Cytokines in the supernatants of stimulated dendritic cells (DCs) with IL-37 were assayed by multiplex immunoassay. Results: An increased level of IL-37 mRNA and protein expression by PBMCs was found in the patient group with clinically active AAU compared to controls. There was no significant difference in IL-37 mRNA and protein expression levels between HLA-B27 associated AAU and idiopathic AAU. IL-37 significantly inhibited the production of IL-1β, IL-6, IL-10, IL-21, IL-23, TNF-α and IFN-γ. IL-37 levels of mRNA and protein expression showed a significant positive correlation with disease activity. Conclusions: Elevated IL-37 expression is associated with disease activity in HLA-B27 associated AAU and idiopathic AAU. IL-37 can inhibit proinflammatory cytokine productions in AAU. Manipulation of IL-37 may offer a new therapeutic target for these entities.