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Abstract
BackgroundInterleukin-37 (IL-37), a new member of IL-1 family cytokine, is recently identified as a natural inhibitor of innate immunity. This study aimed to measure the peripheral blood mononuclear cells (PBMCs) and serum levels of IL-37 in patients with systemic lupus erythematosus (SLE) and to investigate its role in SLE, including its correlation with disease activity, organ disorder and the regulation of inflammatory cytokines.MethodsThe expressions of IL-37 mRNAs in PBMCs and serum IL-37 levels in 66 SLE patients were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). SLE patients PBMCs were stimulated with recombinant IL-37, levels of cytokines TNF-α, IL-1β, IL-6 and IL-10 were detected by RT-PCR and ELISA.ResultsIL-37 mRNAs and serum protein levels were higher in patients with SLE compared with healthy controls. Patients with active disease showed higher IL-37 mRNAs and serum protein levels compared with those with inactive disease as well as healthy controls. Serum IL-37 levels correlated with SLEDAI and inversely with C3 and C4. Serum IL-37 levels were higher in SLE patients with renal involvement compared with those without renal disease. In vitro, IL-37 inhibited the production of TNF-α, IL-1β and IL-6 in PBMCs of patients with SLE, whereas the production of IL-10 was unaffected.ConclusionsIL-37 associated with SLE disease activity, especially related with SLE renal disease activity. IL-37 is an important cytokine in the control of SLE pathogenesis by suppressing the production of inflammatory cytokines. Thus, IL-37 may provide a novel research target for the pathogenesis and therapy of SLE.
Highlights
Interleukin-37 (IL-37), a new member of IL-1 family cytokine, is recently identified as a natural inhibitor of innate immunity
Recent studies demonstrated that anti-inflammatory cytokines TGF-β, IL-10, several toll-like receptor (TLR) ligands and pro-inflammatory cytokines such as IL-1β, Tumor necrosis factor (TNF)-α, IFN-γ and IL-18 induce IL-37 production in peripheral blood mononuclear cells (PBMCs) [4,5]
IL-37 mRNAs and serum protein levels were higher in patients with systemic lupus erythematosus (SLE) compared with healthy controls The expressions of IL-37 mRNAs in PBMCs and Serum IL-37 protein levels from 66 SLE patients and 41 ageand sex-matched healthy controls (HC) were measured by RT-polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively
Summary
Interleukin-37 (IL-37), a new member of IL-1 family cytokine, is recently identified as a natural inhibitor of innate immunity. Recent studies demonstrated that anti-inflammatory cytokines TGF-β, IL-10, several toll-like receptor (TLR) ligands and pro-inflammatory cytokines such as IL-1β, TNF-α, IFN-γ and IL-18 induce IL-37 production in peripheral blood mononuclear cells (PBMCs) [4,5]. Similar studies have found that IL-37 was not detected in the normal colonic mucosa, but in the inflamed mucosa of IBD patients [9]. These findings tend to imply that IL-37 mediates a negative feedback mechanism to suppress excessive inflammation
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