Abstract
BackgroundInterleukin-37 (IL-37) has been known to play an immunosuppressive role in various inflammatory disorders, but whether it participates in the regulation of pathogenesis of ankylosing spondylitis (AS) has not been investigated. Here, we examined the serum levels of IL-37 and its clinical association in AS, and explored the anti-inflammatory effects of IL-37 on peripheral blood mononuclear cells (PBMCs) from AS patients.MethodsThe mRNA levels of IL-37, TNF-α, IL-6, IL-17, and IL-23 in PBMCs and their serum concentrations from 46 AS patients were examined by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunoassay (ELISA), respectively. The correlations between serum IL-37 levels with disease activity, laboratory values and pro-inflammatory cytokines in AS were analyzed by Spearman correlation test. PBMCs from 46 AS patients were stimulated with recombinant IL-37 protein, expressions of TNF-α, IL-6, IL-17 and IL-23 were determined by RT-PCR and ELISA.ResultsCompared to healthy controls (HC), AS patients and active AS patients showed higher levels of IL-37 in PBMCs and serum respectively. Strikingly, serum IL-37 levels were higher in AS patients with osteoporosis than those without. Serum levels of IL-37 were correlated with laboratory values as well as TNF-α, IL-6 and IL-17, but not IL-23 in patients with AS. The productions of pro-inflammatory cytokines such as TNF-α, IL-6, IL-17, IL-23 in PBMCs from AS patients were obviously attenuated after recombinant IL-37 stimulation, but not in the HC.ConclusionThe higher levels of IL-37 were found in AS patients, which were correlated with disease activity and AS related pro-inflammatory cytokines. More importantly, IL-37 inhibits the expressions of the pro-inflammatory cytokines from PBMCs in AS patients, indicating the potential anti-inflammatory role of IL-37 in AS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0394-3) contains supplementary material, which is available to authorized users.
Highlights
Interleukin-37 (IL-37) has been known to play an immunosuppressive role in various inflammatory disorders, but whether it participates in the regulation of pathogenesis of ankylosing spondylitis (AS) has not been investigated
Elevated expression of IL-37 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with AS especially patients with active AS To investigate the association between IL-37 levels and AS, IL-37 mRNA expression in PBMCs from AS patients and healthy controls was detected by real-time polymerase chain reaction (RT-PCR)
Associations of serum IL-37 with pro-inflammatory cytokines levels Published studies demonstrated that pro-inflammatory cytokines IL-17, Tumor necrosis factor-α (TNF-α), IL-6 and IL-23 play an important role in promoting disease development of AS [5,6,7,8,9,10,11]. Consistent with these findings, we demonstrated that the levels of serum IL-17, TNF-α, IL-6 and IL-23 were significantly higher in patients with AS than healthy controls
Summary
Interleukin-37 (IL-37) has been known to play an immunosuppressive role in various inflammatory disorders, but whether it participates in the regulation of pathogenesis of ankylosing spondylitis (AS) has not been investigated. We examined the serum levels of IL-37 and its clinical association in AS, and explored the anti-inflammatory effects of IL-37 on peripheral blood mononuclear cells (PBMCs) from AS patients. Ankylosing spondylitis (AS) is a prevalent chronic inflammatory disease characterized by chronic inflammation in the axial skeleton and peripheral joints respectively and leading to bone erosion, which seriously influences the quality life of patients [1]. The etiology of AS is unclear, accumulating evidences have underlined that the levels of proinflammatory cytokines (TNF-α, IL-6, IL-17 and IL-23) were significantly increased in the peripheral blood of AS patients [6,7,8,9,10,11,12]. Clinical trials suggested that blocking these cytokines could partly relieve inflammatory symptoms of AS and appears to reduce disease severity [13,14,15]. Recent studies have indicated that IL-37 downregulated the expressions of pro-inflammatory cytokines in chronic inflammatory diseases such as system lupus erythematosus (SLE) [16], rheumatoid arthritis (RA) [17] and inflammatory bowel disease [18], suggesting IL-37
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