Increased levels of interleukin-33 associated with bone erosion and interstitial lung diseases in patients with rheumatoid arthritis

Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shen Yang 110001, China.
Cytokine (Impact Factor: 2.66). 04/2012; 58(1):6-9. DOI: 10.1016/j.cyto.2011.12.010
Source: PubMed


To analyze the levels of interleukin-33 (IL-33) in the serum of patients with rheumatoid arthritis (RA) and investigated its possible pathophysiological importance.
The concentrations of IL-33 and matrix metalloproteinase (MMP)-3 were measured by enzyme-linked immunosorbent assay (ELISA) in the serum of 121 patients with RA and 47 controls. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anticyclic citrullinated peptide (anti-CCP) were measured by standard laboratory techniques. Interstitial lung disease (ILD) was identified on high-resolution computed tomography. Disease activity in RA was scored with the Disease Activity Score 28 based on C-reactive protein levels (DAS28-CRP). The bone erosion of RA patients was evaluated by modified Sharp Score (MSS).
Serum levels of IL-33 and MMP-3 were significantly higher in RA patients than in healthy controls. Significant higher levels of IL-33 were found in CCP-positive group and in patients with ILD. There was positive correlation between the levels of IL-33 and RF. Moreover, there was also positive correlation between IL-33 and MMP-3, MSS.
These data support the hypothesis that IL-33 may be involved in RA pathogenesis and it may partly contribute to the bone erosion in RA patients.

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    • "However, the same group found that in STEMI patients elevated IL-33 was associated with increased 30-days and 1-year mortality [24]. Moreover, circulating IL-33 levels were shown to be increased in patients with different immune-inflammatory diseases such as rheumatoid disorders [23] [41], systemic sclerosis [42], and ulcerative colitis [43]. Some limitations of the present study have to be acknowledged. "
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    ABSTRACT: The study aim was to determine the predictive value of interleukin (IL)-33, a recently described member of the IL-1 family of cytokines, for the development of in-stent restenosis (ISR). IL-33 serum levels were measured in 387 consecutive patients undergoing percutaneous coronary intervention (PCI) of whom 193 had stable angina, 93 non-ST elevation myocardial infarction (NSTEMI), and 101 ST-elevation MI (STEMI), respectively. Blood was taken directly before and 24 h after stent implantation. The presence of ISR was initially evaluated by clinical means after six to eight months. When presence of myocardial ischemia was suspected, coronary angiography was performed to confirm the suspected diagnosis of ISR. Clinical ISR was present in total in 34 patients (8.8%). IL-33 was detectable in 185 patients and was below detection limit in 202 patients. In patients with decreased IL-33 (n = 95), unchanged or non-detectable levels (n = 210) or increased levels of IL-33 after PCI (n = 82), ISR-rate was 2.1%, 9.5% and 14.6%, respectively (p < 0.05). Accordingly, patients with ISR showed a significant increase of IL-33 upon PCI (p < 0.05). This association was independent from clinical presentation and risk factors as well as numbers and type of stents. In patients with both stable and unstable coronary artery disease, an increase of IL-33 serum levels after stent implantation is associated with a higher rate of in-stent restenosis.
    Cytokine 06/2014; 67(2):65–70. DOI:10.1016/j.cyto.2014.02.014 · 2.66 Impact Factor
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    • "In patients with RA, immunohistochemistry and in situ hybridization have identified IL-33 residing in the synovial cells of inflamed joints [5]. The level of IL-33 was elevated in both serum and synovial fluid and associated with autoantibody production, bone erosion, and interstitial lung disease [6,7]. In a murine model, IL-33 could exacerbate collagen-induced arthritis (CIA) and elevate the production of proinflammatory cytokines and anticollagen antibodies [8]. "
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    ABSTRACT: Interleukin (IL)-33 is a proinflammatory cytokine contributing to the pathogenesis of rheumatoid arthritis (RA). The gene encoding IL-33 may serve as a genetic factor and be associated with the risk of RA. To investigate the potential association between IL33 and RA, we performed a case-control study based on Chinese Han population. A three-stage case-control study was performed. Two tag single-nucleotide polymorphisms (SNPs) (rs7044343 and rs10975514) mapping to the IL33 gene were first genotyped in the discovery population. We further genotyped rs7044343 and rs10975514 in the validation and replication population. The associations between the two tag SNPs and phenotypic subgroups of RA and levels of serum IL-33 were assessed by logistic regression model. In the discovery population, the CC genotype of rs7044343 was associated with RA patients (Odds ratio (OR) = 0.777, 95% confidence intervals (CI) 0.611 to 0.988, P = 0.040). After anti-citrullinated peptide antibody (ACPA) stratification, the CC genotype of rs7044343 was also showed to be a protective genotype in RA without ACPA (OR = 0.610, 95% CI 0.379 to 0.982, P = 0.042). In the validation population and replication population, the association between rs7044343 and RA, especially ACPA-negative RA was still significant. A meta-analysis of discovery, validation and replication panels conferred the association between CC genotype of rs7044343 and RA (Pcombined = 0.0004; ORcombined = 0.77, 95% CI 0.67 to 0.89). There was no evidence for heterogeneity between three sample sets (Phet = 0.99, I2 = 0%). Similar results were also obtained in ACPA-negative RA (Pcombined = 0.0002; ORcombined = 0.57, 95% CI 0.43 to 0.77). No association was detected between rs10975514 polymorphism and RA susceptibility in the discovery and validation population. The serum levels of IL-33 were significantly lower in the patients with rs7044343 CC genotype. The CC genotype of rs7044343 in IL33 is associated with RA patients and downregulates IL-33 expression in RA.
    Arthritis research & therapy 04/2014; 16(2):R105. DOI:10.1186/ar4554 · 3.75 Impact Factor
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    • "Interestingly, increased levels of IL-33 in RA patients were correlated with interstitial lung diseases and bone erosion [30] "
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    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.
    Mediators of Inflammation 02/2014; 2014:342410. DOI:10.1155/2014/342410 · 3.24 Impact Factor
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