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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01 Jan 2016
TL;DR: Genes common to all four atopic phenotypes, especially genes that are part of the adaptive and innate immune response and skin barrier dysfunction, may help to explain the molecular processes underlying the sequential appearance of the clinical manifestations characteristic of the atopic march.
Abstract: Significant advancements in the field of genetic epidemiology over the past several decades have greatly expanded our understanding of the pathogenesis of the atopic phenotypes. To date, multiple genome-wide linkage, candidate gene, and genome-wide association studies have elucidated genes (and in some cases, causal variants) associated with atopic dermatitis, allergic rhinitis, childhood asthma, and, to a lesser degree, food allergy, and these findings have been replicated in independent and often ethnically and racially diverse populations. Despite the complexities associated with coexisting phenotypes and environmental influences, genes common to all four atopic phenotypes, especially genes that are part of the adaptive and innate immune response and skin barrier dysfunction, may help to explain the molecular processes underlying the sequential appearance of the clinical manifestations characteristic of the atopic march.
7 citations
Patent•
21 Apr 2015TL;DR: In this article, compositions and methods for treating a cytokine release syndrome such as chimeric antigen receptor T-cell cytokines release syndrome or hemophagocytic lymphohistiocytosis are provided.
Abstract: Compositions and methods for treating a cytokine release syndrome such as chimeric antigen receptor T-cell cytokine release syndrome or hemophagocytic lymphohistiocytosis are provided
6 citations
TL;DR: Results indicate that serum IL-33 levels in RF + poly-JIA patients correlated with disease activity, suggesting a potential role of IL- 33 as a promising indicator of disease activity.
Abstract: Objective: To investigate clinical usefulness of serum interleukin (IL)-33 levels as an indicator of disease activity in juvenile idiopathic arthritis (JIA)Methods: We measured serum levels of IL-33 in 39 patients with JIA, including 7 patients with rheumatoid factor positive poly-JIA (RF + poly-JIA), 8 patients with RF negative poly-JIA (RF-poly-JIA), 20 patients with oligoarticular JIA (Oligo-JIA), 4 patients with enthesitis-related arthritis (ERA) and 30 age-matched healthy controls Furthermore, we determined their correlation with measures of disease activityResults: Serum IL-33 levels in patients with RF + poly-JIA were significantly elevated compared to those in patients with RF-poly-JIA, oligo-JIA and HC Serum IL-33 levels in patients with RF-poly-JIA, oligo-JIA and ERA were not elevated compared to those in HC Serum IL-33 levels in RF + poly-JIA patients normalized in remission phase Serum IL-33 levels correlated positively with RF in patients with RF + poly-JIAConclusions: These re
6 citations
TL;DR: IL-33 may contribute to the inflammation in the airways by acting on airway smooth muscle cells, and IL-33 and ST2 may play important roles in allergic bronchial asthma.
Abstract: Background: Although it is recognized that IL-33 plays a key role in the onset of asthma, it is currently unclear whether IL-33 acts on any other target cells besides mast cells and Th2 cells in asthma. We investigated that whether airway smooth muscle cells (ASMCs) could contribute to asthma via stimulation with IL-33 . Methods: To create a mouse model of acute asthma , murine ASMCs were isolated and cultured in vitro with IL-33. The ASMCs were divided into two groups, ASMCs from normal mice and ASMCs from ovalbumin-se n sitized mice. The release of mouse KC was analyzed by PCR and ELISA. I mmuno cy tochemical Staining of murine ASMCs for ST2 and IL-1RAcP was performed. Results: IL-33 promote d KC expression, both in terms of mRNA and protien levels, in ASMCs from ovalbumin-se n sitized mice . ST2 and IL-1RAcP were expressed in the membrane of ASMCs in ovalbumin-se n sitized mice . Conclusion: IL-33 may contribute to the inflammation in the airways by acting on airway smooth muscle cells. IL-33 and ST2 may play important roles in allergic bronchial asthma.
5 citations
TL;DR: Results indicate that the IL-33-neutralizing antibody may provide a therapeutic strategy for RA by inhibiting the release of proinflammatory cytokines.
Abstract: Rheumatoid arthritis (RA) is considered a systemic chronic inflammatory joint disease characterized by chronic synovitis and cartilage and bone destruction. Interleukin-33 (IL-33) is a proinflammatory cytokine which is highly expressed in the synovium of RA patients and the joints of mice with collagen-induced arthritis (CIA) and exacerbates CIA in mice. However, the role of the IL-33-neutralizing antibody in the murine model of CIA remains unclear. In the present study, CIA mice were given intraperitoneally with polyclonal rabbit anti-murine IL-33 antibody (anti-IL-33) or normal rabbit IgG control after the first signs of arthritis. Administration of anti-IL-33 after the onset of disease significantly reduced the severity of CIA and joint damage compared with controls treated with normal rabbit IgG. Anti-IL-33 treatment also significantly decreased the serum levels of interferon-γ(IFN-γ),IL-6, IL-12, IL-33, and tumor necrosis factor-α (TNF-α). Moreover, anti-IL-33 treatment significantly downregulated the production of IFN-γ, IL-6, IL-12, IL-33, and TNF-α in ex vivo-stimulated spleen cells. Together, our results indicate that the IL-33-neutralizing antibody may provide a therapeutic strategy for RA by inhibiting the release of proinflammatory cytokines.
5 citations
Cites background from "Measurement of interleukin-33 (IL-3..."
...[35] found that there is a significant positive correlation between IL-33 and IL-6 levels in the RA sera....
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...IL-33 was highly expressed in human RA synovium [35]....
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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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