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.
Citations
More filters
TL;DR: Biomarker panels for frailty would be of high value and better than single markers.
267 citations
Cites background from "Measurement of interleukin-33 (IL-3..."
...Interestingly, serum levels of ST2 are higher in rheumatoid arthritis patients than in healthy controls and are decreased following treatment with conventional disease-modifying antirheumatic drugs (Hong et al., 2011)....
[...]
TL;DR: The main functions of the IL-1 family are innate immune reactions and inflammation, rather than acquired immunity, which can occur in several rheumatic diseases.
Abstract: More than any other cytokine family, the 11 members of the IL-1 family are associated with innate immune responses, which occur in acute inflammation and chronic inflammatory conditions such as rheumatic diseases. In many rheumatic diseases, the severity of the condition can result from the balance between the pro-inflammatory and anti-inflammatory members of the IL-1 family. Pro-inflammatory family members (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β and IL-36γ) are found in the articular environment during arthritis and often correlate with the degree of inflammation present. IL-1β has emerged as pivotal for promoting inflammation, particularly in autoinflammatory diseases, whereas IL-1α and the IL-36 subfamily are associated with skin diseases. IL-33 regulates T helper 2 (TH2) cell-mediated diseases, in sharp contrast to IL-18, which mainly regulates TH1 cell-mediated responses. The IL-1 family also contains four members that suppress inflammation: two specific receptor antagonists (IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra)), and two members that broadly suppress innate inflammation by non-specifically reducing several cytokines and chemokines (IL-37 and IL-38). In this Review, each of the eleven IL-1 family cytokines and their receptors are discussed, along with their putative roles in rheumatic disease and therapeutic options for targeting or promoting these cytokines. Cytokines from the IL-1 family perform important functions in innate immune reactions, but can also be involved in chronic inflammatory diseases. This Review highlights the roles of IL-1 family members in rheumatic diseases and potential therapeutic approaches to targeting them.
223 citations
TL;DR: This review summarizes new data on inflammatory bone loss obtained in 2011 and describes the molecular pathways by which receptor activator of nuclear factor-κB ligand and RANKL induce osteoclast differentiation.
Abstract: Chronic inflammation including autoimmune disease is an important risk factor for the development of osteoporosis. Receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) play a central role in osteoclast differentiation and function, and the molecular pathways by which M-CSF and RANKL induce osteoclast differentiation have been analyzed in detail. Proinflammatory cytokines directly or indirectly regulate osteoclastogenesis and bone resorption providing a link between inflammation and osteoporosis. Tumor necrosis factor-α, interleukin (IL)-1, IL-6, and IL-17 are the most important proinflammatory cytokines triggering inflammatory bone loss. Inhibition of these cytokines has provided potent therapeutic effects in the treatment of diseases such as rheumatoid arthritis. Further investigation is needed to understand the pathophysiology and to develop new strategies to treat inflammatory bone loss. This review summarizes new data on inflammatory bone loss obtained in 2011.
152 citations
TL;DR: Current knowledge regarding the roles of IL‐33 in the functions of various cell types and the pathogenesis of allergy suggests that it acts as an alarmin, like IL‐1α and high‐mobility group box chromosomal protein‐1 (HMGB‐1).
Abstract: Interleukin-33 (IL-33) is a member of the IL-1 cytokine family, which includes IL-1 and IL-18, and is considered to be important for host defense against nematodes by inducing Th2 cytokine production via the IL-33 receptor IL-33 receptor is a heterodimer of IL-1 receptor-like 1 (IL-1RL1; also called ST2, T1, Der4, and fit-1) and IL-1 receptor accessory protein (IL-1RAcP) On the other hand, excessive and/or inappropriate production of IL-33 is considered to be involved in the development of various disorders, such as allergic and autoimmune diseases Unlike IL-1β and IL-18, IL-33 does not seem to be secreted through the activation of inflammasomes in events such as apoptosis However, IL-33 is localized in the nucleus of cells and is released during tissue injury associated with necrosis This suggests that it acts as an alarmin, like IL-1α and high-mobility group box chromosomal protein-1 (HMGB-1) This review summarizes current knowledge regarding the roles of IL-33 in the functions of various cell types and the pathogenesis of allergy
107 citations
Cites background from "Measurement of interleukin-33 (IL-3..."
...The serum IL-33 levels were significantly higher in patients with rhinitis and/or conjunctivitis caused by Japanese cedar pollens than in healthy subjects (126, 128)....
[...]
TL;DR: The role of soluble ST2 as a HF biomarker will be discussed, specifically addressing analytical considerations of measuring sST2 as well as the clinical applications of measurement of s ST2 for the diagnosis, prognosis and monitoring of acute and chronic HF.
106 citations
References
More filters
TL;DR: It is shown that the distal but not proximal ST2L promoter is responsible for specific gene expression in Th2 cells and that the reduced expression of ST1/ST2L in response to high doses of antigen is also reversed by the neutralization of IFN‐γ.
Abstract: T1/ST2L, an IL-1 receptor homologue, is selectively expressed on murine Th2 cells and specific anti-ST2L antibodies can profoundly modulate the Th1/Th2 balance in vivo. Naive CD4(+) T cells do not express ST2L but do so on activation with specific antigen in the presence of IL-4 or when stimulated with low doses of antigen in the absence of exogenously added IL-4. Similarly enhanced ST2L expression occurred after stimulation of Th2 cells with antigen or the mitogen ConA in the presence of APC. Restimulation of Th2 cells in the presence of IFN-gamma led to a decreased expression of ST2L to below basal levels. Conversely, Th2 cells cultured with IL-4 led to increased ST2L expression. The reduced expression of ST2L in response to high doses of antigen is also reversed by the neutralization of IFN-gamma. Using an ST2L promoter/luciferase reporter gene construct, we show that the distal but not proximal ST2L promoter is responsible for specific gene expression in Th2 cells. IL-4 enhances, whereas IFN-gamma suppresses ST2L expression via direct modulation of the distal promoter of the ST2L gene. These data provide a mechanistic explanation for the selective expression of ST2L on Th2 cells.
37 citations
"Measurement of interleukin-33 (IL-3..." refers background in this paper
...For example, IL-4 enhances and IFN-γ suppresses ST2L expression on Th2 cells (22)....
[...]