IL-37 inhibits the production of inflammatory cytokines in peripheral blood mononuclear cells of patients with systemic
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RESEARCH
Open Access
IL-37 inhibits the production of inflammatory cytokines in peripheral blood mononuclear cells of patients with systemic lupus erythematosus: its correlation with disease activity Liang Ye1,2,3, Ling Ji4, Zhongyang Wen1,2,3, Yanfei Zhou1,3, Dongsheng Hu5, Yanqun Li1,2,3, Ting Yu1,2,3, Bingni Chen1,2,3, Jinshun Zhang1,2,3, Liping Ding1,2,3, Jing Du4* and Zhong Huang1,2,3*
Abstract Background: Interleukin-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. Methods: The 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. Results: IL-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. Conclusions: IL-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. Keywords: Interleukin-37, Systemic lupus erythematosus, Autoimmunity, Cytokines, Peripheral blood mononuclear cell
Background The interleukin (IL)-1 family of cytokines possesses a variety of immunoregulatory properties in response to inflammation and autoimmune diseases [1]. As the members of the IL-1 family, seven cytokines (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β and IL-36γ) act as agonists, and two are classified as naturally occurring receptor antagonists (IL-1Ra and IL-36Ra) [2,3]. IL-37, the most recently identified IL-1 member, originally defined * Correspondence: [email protected]; [email protected] 4 Department of laboratory medicine, Peking University Shenzhen Hospital, 518036 Shenzhen, China 1 Biological therapy institute, Shenzhen University School of Medicine, 518060 Shenzhen, China Full list of author information is available at the end of the article
as IL-1 family member 7 (IL-1F7), is a fundamental inhibitor of innate immunity [4
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