Abstract
BackgroundIntreleukin-37 (IL-37), a member of IL-1 family, is primarily an anti-inflammatory cytokine, which reduces systemic and local inflammation. However, the expression and role of IL-37 in Graves' disease (GD) remains unknown. This study aims to measure the levels of serum and peripheral blood mononuclear cells (PBMCs) IL-37 in patients with Graves' disease and to examine its association with disease activity. Furthermore, we investigate the effect of IL-37 on proinflammatory cytokines involved in the pathogenesis of GD.MethodsThe expressions of IL-37, TNF-α, IL-6, and IL-17 mRNA in peripheral blood mononuclear cells (PBMCs) of 40 patients with Graves' disease were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the levels of IL-37, TNF-α, IL-6, and IL-17 in serum were detected by enzyme-linked immunoassay (ELISA). The correlation of serum IL-37 levels with cytokines and disease activity in Graves' disease patients were investigated. The expressions of cytokines TNF-α, IL-6, and IL-17 in PBMCs under recombinant IL-37 stimulation were determined by RT-PCR and ELISA respectively.ResultsThe levels of IL-37, TNF-α, IL-6, and IL-17 in PBMCs and serum were significantly increased in patients with GD compared with healthy controls (HC). Serum IL-37 were closely correlated with TNF-α, IL-6, IL-17, thyrotropin (TSH), free thyroxine (FT4),free triiodothyronine (FT3) and thyrotropin receptor antibody (TRAB). GD patients with active disease showed higher IL-37 mRNA and serum protein levels compared with those with inactive disease as well as HC. Moreover, IL-37 suppressed the production of IL-6, IL-17 and TNF-α in PBMCs of patients with GD.ConclusionsIncreased level of IL-37 in patients with GD are associated with TNF-α, IL-6, IL-17 and disease activity, and it plays a protective role against inflammatory effect in GD by inhibiting the production of proinflammatory cytokines. Thus, IL-37 may provide a novel research target for the pathogenesis and therapy of GD.
Highlights
Graves’ disease (GD) is an organ-specific autoimmune disease characterized by the production of agonistic auto antibodies against the thyroid-stimulating hormone receptor (TSHR), which mimic the stimulatory effects of TSH, leading to hyperthyroidism and diffuse hyperplasia of the thyroid gland [1,2,3]
Recent research shown that the percentages of Th17 and the levels of plasma IL-17 in GD patients were correlated positively with the levels of serum TRAb in these patients, suggesting that IL-17 may contribute to the pathogenesis of GD in Chinese [15].Serum IL-6, TNF-a and IL-17 levels correlated strongly with thyroid endocrine status and disease activity, indicating that they play pivotal roles in the pathogenesis of GD [17,18,19]
The results showed that serum IL-37 levels in GD patients were significantly higher than those from healthy controls (HC) (Fig. 1A, p = 0.0006)
Summary
Graves’ disease (GD) is an organ-specific autoimmune disease characterized by the production of agonistic auto antibodies against the thyroid-stimulating hormone receptor (TSHR), which mimic the stimulatory effects of TSH, leading to hyperthyroidism and diffuse hyperplasia of the thyroid gland [1,2,3]. The pathogenesis of the disease remains elusive, evidences indicated that destruction of the balance of pro- and anti- inflammatory cytokines result in thyroid lymphocytic infiltration and B cell activation that produce autoimmune antibodies against thyroid antigens, which in turn played an important role in the pathogenesis of GD [1]. It has been shown that antithyroid drugs reduce the production of thyroidal pro-inflammatory cytokines contributing to remit the inflammation of GD [1]. This study aims to measure the levels of serum and peripheral blood mononuclear cells (PBMCs) IL-37 in patients with Graves’ disease and to examine its association with disease activity. We investigate the effect of IL-37 on proinflammatory cytokines involved in the pathogenesis of GD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
