Measurement of interleukin-33 (IL-33) and IL-33 receptors (sST2 and ST2L) in patients with rheumatoid arthritis.
01 Sep 2011-Journal of Korean Medical Science (Korean Academy of Medical Sciences)-Vol. 26, Iss: 9, pp 1132-1139
TL;DR: IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA, and the levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-naïve RA.
Abstract: The interleukin-33 (IL-33)/ST2 pathway has emerged as an intercellular signaling system that participates in antigen-allergen response, autoimmunity and fibrosis. It has been suggested that IL-33/ST2 signaling has been involved in the pathogenesis of rheumatoid arthritis (RA), because IL-33 and its receptor have been specifically mapped to RA synovium. The aim of this study was to determine the levels of IL-33 and sST2 in sera and synovial fluids in patients with RA. The serum level of IL-33 was significantly higher in patients with RA (294.9 ± 464.0 pg/mL) than in healthy controls (96.0 ± 236.9 pg/mL, P = 0.002). The synovial fluid level of IL-33 was significantly higher in RA patients than in osteoarthritis patients. The level of serum sST2 was higher in RA patients than in healthy controls (P = 0.042). A significant relationship was found between the levels of IL-33 and IL-1β (r = 0.311, P = 0.005), and IL-33 and IL-6 (r = 0.264, P = 0.017) in 81 RA patients. The levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-naive RA. Conclusively, IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA.
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TL;DR: This study suggests that parts of the novel members of IL-1 family cytokines were involved in the pathogenesis of RA, and may provide a novel target for therapies of RA.
Abstract: The interleukin (IL)-1 family of cytokines comprises 11 members, including 7 pro-inflammatory cytokines (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β,IL-36γ) and 4 anti-inflammatory cytokines (IL-1R antagonist (IL-1Ra), IL-36Ra, IL-37 and IL-38), and play central roles in mediating immune responses. In this study, we detected serum levels of IL-36 subfamily cytokines (including IL-36α, IL-36β, IL-36γ, IL-36Ra and IL-38), IL-37, IL-33 and aimed to investigate the roles of these cytokines in rheumatoid arthritis (RA) preliminarily. A total of 10 RA patients and 10 healthy controls (HCs) were involved in this study, we measured IL-36 subfamily cytokines, IL-37 and IL-33 levels in the serum of the experiment subjects by QAH-IL1F-1 assay. Clinical and laboratory data of the subjects were collected and analyzed by Spearman's rank test. Compared to that of HCs, IL-36α, IL-36β, IL-36Ra, IL-38 and IL-33 levels were significantly increased in RA patients. We also found RA patients with elevated IL-36Ra had a higher ESR and RF-IgM, and there was a positive correlation between increased IL-36α and CRP. Our study suggests that parts of the novel members of IL-1 family cytokines were involved in the pathogenesis of RA, and may provide a novel target for therapies of RA.
32 citations
Cites background from "Measurement of interleukin-33 (IL-3..."
...Yeon-Sik Hong, Su-Jin Moon, Young-Bin Joo, Chan-Hong Jeon, Mi-La Cho, Ji Hyeon Ju, Hye-Jwa Oh, Yu-Jung Heo, Sung-Hwan Park, Ho-Youn Kim and Jun-Ki Min....
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...Yeon-Sik Hong (31) found that serum level of IL-33 correlated with that of IL-1β and IL-6....
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TL;DR: It is demonstrated that the inhibitory effect of IL-10 in suppressing IL-33 production requires STAT3 activation in macrophages, suggesting a potential therapeutic role of IL/ST2 signaling pathways in vivo in autoimmune diseases.
Abstract: // Si Chen 1,2,* , Bingni Chen 1,2,3,* , Zhongyang Wen 1,2,3,* , Zhong Huang 1,2,3 and Liang Ye 1,2,3 1 Institute of Biological Therapy, Shenzhen University, Shenzhen, China 2 Department of Pathogen Biology and Immunology, Shenzhen University School of Medicine, Shenzhen, China 3 Shenzhen City Shenzhen University Immunodiagnostic Technology Platform, Shenzhen, China * These authors have contributed equally to this work Correspondence to: Liang Ye, email: // Zhong Huang, email: // Keywords : IL-33, IL-33 receptor, IL-10, macrophage, rheumatoid arthritis, Immunology and Microbiology Section, Immune response, Immunity Received : August 11, 2016 Accepted : March 01, 2017 Published : March 16, 2017 Abstract IL-10 is an immunosuppressive cytokine produced and sensed by many immune cells and exerts a protective role in autoimmune diseases. However, the underlying mechanism by which IL-10 contributes to prevent the arthritic inflammation in macrophages is poorly understood. Herein we report on a novel anti-arthritic property of IL-10 through the inhibition of IL-33 signaling by macrophages during collagen-induced arthritis (CIA) development. We show that IL-33 expression rather than its receptor (ST2) is positively correlated with IL-10 level in active RA. IL-10 deficiency in mice leads to significant upregulation of IL-33 expression and aggravates the progression of CIA, while exogenous IL-10 treatment effectively diminishes IL-33 production in IL-10 knockout (IL-10 -/- ) CIA mice. We demonstrate further that the inhibitory effect of IL-10 in suppressing IL-33 production requires STAT3 activation in macrophages. Furthermore, IL-33 stimulated proinflammatory genes are notably increased in IL-10 -/- CIA mice, whereas macrophages treated with recombinant IL-10 exhibit decreased IL-33 amplified inflammation and inhibited IL-33 activated NF-κB signaling pathway. Our findings indicate that IL-10 act as a negative regulator of IL-33/ST2 signaling pathways in vivo , suggesting a potential therapeutic role of IL-10 in autoimmune diseases.
31 citations
Cites background from "Measurement of interleukin-33 (IL-3..."
...com/oncotarget The expression levels of IL-33 and ST2 seem to correlate with RA disease activity [8]....
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...Recent reports have found increased IL-33 and ST2 production in the serum and synovial tissue of patients with RA [8, 9]....
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...To extend the knowledge about the previously reported that upregulated IL-33 and ST2 expression and increased IL-10 production could be detected in patients with RA and involved in the pathogenesis of RA [8, 14], we initially wanted to investigate the possible correlation between IL-33/ST2 and IL-10 in RA....
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TL;DR: It is demonstrated that IL-33 and sST2 are highly expressed in patients with Behcet's disease and that serum s ST2 is an independent factor associated with IBDDAM and BDCAF, suggesting a potential role for sST 2 as a surrogate marker of disease activity in patientswith BD.
Abstract: Interleukin (IL)-33 is an important mediator of innate immunity. Behcet's disease (BD) is an autoinflammatory disorder characterized by hyperactivity of the innate immune response. We measured serum levels of IL-33 and its receptor soluble ST2 (sST2) in patients with BD to investigate their association with disease activity. Serum levels of both IL-33 and sST2 were higher in patients with BD compared with those in normal controls (IL-33: 594.48±175.04 pg/mL in BD and 224.23±56.64 pg/mL in normal controls [P=0.048], sST2: 99.01±15.92 pg/mL in BD and 23.56±3.25 pg/mL in normal controls [P<0.001]). IL-33 and sST2 expression in skin tissue, as shown by immunohistochemistry, was higher in patients with BD compared with that in the normal controls. Serum sST2 level correlated significantly with the BD currently active form (BDCAF), Iranian BD dynamic activity measure (IBDDAM), erythrocyte sedimentation rate and C-reactive protein. Multiple linear regression showed that serum sST2 was an independent factor associated with IBBDAM (regression coefficient, 0.374; P=0.004), and BDCAF (regression coefficient, 0.236; P=0.047). These results demonstrate that IL-33 and sST2 are highly expressed in patients with BD and that serum sST2 is an independent factor associated with IBDDAM and BDCAF, suggesting a potential role for sST2 as a surrogate marker of disease activity in patients with BD.
30 citations
Cites background from "Measurement of interleukin-33 (IL-3..."
...Furthermore, antirheumatic drugs treatments such as diseasemodifying antirheumatic drugs and etanercept reduce serum levels of IL-33, sST2, and CRP in patients with RA (13-15)....
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...(13) reported that serum levels of IL-33 and sST2 are correlated with IL-1β and IL-6....
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TL;DR: This work hypothesizes a possible role of IL-33 in periodontal disease and bone loss and examines the implications in bone biology and immune response.
Abstract: Interleukin-33 (IL-33) is a recently described member of the IL-1 family. IL-33 acts as an alarmin, chemoattractant, and nuclear factor. ST2, a member of the Toll-like receptor/IL-1R superfamily, the receptor of IL-33, triggers a plethora of downstream effectors and leads the activation of NFK-B, leading the expression of several genes. IL-33 and ST2 are expressed in the majority of cell types, and the IL-33/ST2 axis has a role in immune response, bone homeostasis, and osteoclastogenesis. Several studies show opposite roles of IL-33 in osteoclastogenesis and the implication in bone biology. Few works studied the role of IL-33 in periodontal disease, but we hypothesize a possible role of IL-33 in periodontal disease and bone loss.
30 citations
Cites background from "Measurement of interleukin-33 (IL-3..."
...IL-1Ra [1, 15, 16, 27] IL-F3 Macrophages [27] (i) Pleiotropic actions [27] (ii) Inhibits the production of metalloproteinases (MMPs) [30, 33] Blocks the activation of osteoclasts [31]...
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...IL-1α [1, 22] IL-1F1 (i) Increased in gingival crevicular fluid (indicative of the severity of PD) [25, 26] (ii) Associated with probing depth and attachment loss [26, 27] (iii) Influx of neutrophils and monocytes [28, 29] (iv) Stimulation of the production of PGE2 [30, 31]...
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...IL-1Ra [1, 15, 16, 27] IL-F3 (i) Inflammatory mediators [27] (ii) Reduction indicates severity of the PD [27]...
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...In the synovium of rheumatoid arthritis (RA) patients, elevated levels of IL-33 and sST2 were detected [27]....
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TL;DR: Serum sST2 levels in patients with s-JIA correlated with disease activity, suggesting a potential role as a promising indicator of disease activity and indicating that ST2 may be an important mediator in s- JIA.
29 citations
References
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TL;DR: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA).
Abstract: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.
19,409 citations
"Measurement of interleukin-33 (IL-3..." refers methods in this paper
...RA was diagnosed based on the American College of Rheumatology 1987 criteria (13)....
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Journal Article•
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for the rheumatic diseases to date, and these new revised classified criteria for rheumatoid arthritis are very important as they should provide understanding of the possibly changing face of rheumatism.
Abstract: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for the rheumatic diseases to date. These new revised classification criteria for rheumatoid arthritis are very important as they should provide understanding of the possibly changing face of rheumatoid arthritis.
8,645 citations
TL;DR: A member of theIL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T( H)2 cells is reported.
3,306 citations
"Measurement of interleukin-33 (IL-3..." refers background in this paper
...It also increases the production of IL-5 and IL-13 by polarized Th2 cells (3) and interferon-γ (IFN-γ) production by both iNKT and NK cells (7)....
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...Mature IL-33 has been reported to mediate its biologic effects via T1/ST2 binding by activating NF-κB and MAP kinase (3)....
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...The expression of ST2L, a membrane-anchored long form, is restricted to the surface of Th2 cells and mast cells (3)....
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...Although recombinant pro-IL-33 is cleaved by recombinant caspase-1 in vitro (3), the in vivo role of caspase-1 in the cleavage of pro-IL-33 remains controversial (27)....
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...Therefore, synovial fibroblasts, endothelial cells, activated DCs, and macrophages may be the main source of IL-33 in synovial fluid from RA patients (3, 15)....
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TL;DR: The current knowledge regarding the role of proinflammatory cytokines in the pathophysiology of OA is discussed and the potential of anticytokine therapy in the treatment of this disease is addressed.
Abstract: Osteoarthritis (OA) is associated with cartilage destruction, subchondral bone remodeling and inflammation of the synovial membrane, although the etiology and pathogenesis underlying this debilitating disease are poorly understood. Secreted inflammatory molecules, such as proinflammatory cytokines, are among the critical mediators of the disturbed processes implicated in OA pathophysiology. Interleukin (IL)-1β and tumor necrosis factor (TNF), in particular, control the degeneration of articular cartilage matrix, which makes them prime targets for therapeutic strategies. Animal studies provide support for this approach, although only a few clinical studies have investigated the efficacy of blocking these proinflammatory cytokines in the treatment of OA. Apart from IL-1β and TNF, several other cytokines including IL-6, IL-15, IL-17, IL-18, IL-21, leukemia inhibitory factor and IL-8 (a chemokine) have also been shown to be implicated in OA and could possibly be targeted therapeutically. This Review discusses the current knowledge regarding the role of proinflammatory cytokines in the pathophysiology of OA and addresses the potential of anticytokine therapy in the treatment of this disease.
1,962 citations
"Measurement of interleukin-33 (IL-3..." refers background in this paper
...IL-1β, TNF and IL-6 seem to be the main proinflammatory cytokines involved in the pathophysiology of OA (19)....
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TL;DR: IL-33 is host-protective against helminth infection and reduces atherosclerosis by promoting TH2-type immune responses but can also promote the pathogenesis of asthma by expanding TH2 cells and mediate joint inflammation, atopic dermatitis and anaphylaxis by mast cell activation.
Abstract: Interleukin-33 (IL-33), a newly described member of the IL-1 family, is expressed by many cell types following pro-inflammatory stimulation and is thought to be released on cell lysis. The IL-33 receptor, consisting of ST2 and IL-1 receptor accessory protein, is also widely expressed, particularly by T helper 2 (T(H)2) cells and mast cells. IL-33 is host-protective against helminth infection and reduces atherosclerosis by promoting T(H)2-type immune responses. However, IL-33 can also promote the pathogenesis of asthma by expanding T(H)2 cells and mediate joint inflammation, atopic dermatitis and anaphylaxis by mast cell activation. Thus IL-33 could be a new target for therapeutic intervention across a range of diseases.
925 citations
"Measurement of interleukin-33 (IL-3..." refers background in this paper
...(24) also proposed that in established RA, IL-33 causes mast cell-mediated inflammation, which amplifies the Th17 cell response....
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...(24) suggested that in early RA, IL-33 produced by synovial fibroblasts and synovial endothelial cells induces a Th2-type response....
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