Cytokines in Rheumatoid Arthritis

Ridderstad, Anna; Abedi‐Valugerdi, Manuchehr; Möller, Erna

doi:10.3109/07853899109148051

Cited by 76 publications

(46 citation statements)

References 39 publications

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“…The involvement of IL-2 signaling in chronic inflammatory and autoimmune diseases (rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes) is controversial (Ridderstad et al 1991;Sadlack et al 1993;Parkes et al 1998;Brennan and McInnes 2008;Chistiakov et al 2008). Certain autoimmune conditions, notably those involving inflammation of neurological tissues such as multiple sclerosis (MS) and uveitis, have been shown to be responsive to anti-IL2Ra antibodies (Dunn 2004;Martin 2008;Yeh et al 2008;Kim 2009;Bielekova and Becker 2010).…”

Section: Autoimmune Diseasementioning

confidence: 99%

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Wilson

Arkin

2010

Current Topics in Microbiology and Immunology

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Section: Autoimmune Diseasementioning

confidence: 99%

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Wilson

Arkin

2010

Current Topics in Microbiology and Immunology

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“…The cause and pathologic processes underlying RA have not yet been fully elucidated. However, it is clear that both the cellular immune system and the cytokine network are subject to profound dysregulations (3,4). The success of an antiproinflammatory cytokine therapy directed against either tumor necrosis factor ␣ (TNF␣) or, to a lesser extent, interleukin-1␤ (IL-1␤) has highlighted the significance of these cytokines in the pathologic progression of RA (5)(6)(7)(8).…”

mentioning

confidence: 99%

Induction of CCL13 expression in synovial fibroblasts highlights a significant role of oncostatin M in rheumatoid arthritis

Hintzen¹,

Quaiser²,

Pap³

et al. 2009

Arthritis & Rheumatism

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Objective. To investigate the molecular mechanisms of CCL13/monocyte chemoattractant protein 4 (MCP-4) chemokine expression through proinflammatory cytokines in different primary human fibroblasts and the contribution of CCL13 to monocyte migration.Methods. Using RNase protection assays and enzyme-linked immunosorbent assays, we quantified the expression of CCL13 compared with that of CCL2/ MCP-1 in primary human fibroblasts. Boyden chamber assays were performed to determine the importance of CCL13 for migration of primary monocytes. Pharmacologic inhibitors as well as small interfering RNA knockdown approaches were used to investigate the signaling pathways regulating CCL13 expression.Results. The interleukin-6 (IL-6)-type cytokine oncostatin M (OSM) was a powerful inducer of CCL13 expression in primary synovial fibroblasts from patients with rheumatoid arthritis (RA) as well as those from healthy control subjects but not in other types of fibroblasts. Neither IL-6 nor tumor necrosis factor ␣ could stimulate the expression of CCL13 in synovial fibroblasts; IL-1␤ was a very weak inducer. Synovial fibroblasts from patients with RA constitutively produced low amounts of CCL13, which was partially dependent on constitutive production of OSM. By investigating the underlying molecular mechanism, we identified STAT-5, ERK-1/2, and p38 as critical factors involved in OSM-dependent transcription and messenger RNA stabilization of CCL13.Conclusion. In contrast to other prominent cytokines involved in the pathogenesis of RA, OSM can strongly up-regulate the expression of CCL13, a chemokine recently identified in the synovial fluid of patients with RA. Despite potent OSM-induced signal transduction in all types of fibroblasts analyzed, only synovial fibroblasts secreted CCL13, which might be indicative of tissue-specific imprinting of different fibroblasts during development.

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“…Recently, various attempts have been carried out in adult RA patients to improve the characterization and understanding of the disease by determination of levels of cytokines andlor their soluble receptors that are critically involved in the inflammatory process (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) t By least-squares regression analysis.…”

mentioning

confidence: 99%

Serum cytokines in juvenile rheumatoid arthritis: correlation with conventional inflammation parameters and clinical subtypes

Mangge

Kenzian

Gallistl

et al. 1995

Arthritis & Rheumatism

175

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Objective. To examine the usefulness of determining extended serum cytokine profiles in patients with juvenile rheumatoid arthritis (JRA), for the purpose of improving differential diagnosis and monitoring disease activity. Methods. In a 2‐year prospective study, serum levels of interleukin‐1β (IL‐1β), soluble IL‐2 receptor (sIL‐2R), IL‐6, IL‐8, tumor necrosis factor α (TNFα), and the p55 soluble TNF receptor (sTNFR) were repeatedly determined by enzyme‐linked immunosorbent assay in 40 patients with JRA, 13 patients with postinfectious arthropathies, and 30 healthy controls. The data were compared with conventional parameters of inflammation, such as C‐reactive protein (CRP), iron and hemoglobin levels, erythrocyte sedimentation rate (ESR), white blood cell (WBC) counts, and platelet counts. WBC subsets were analyzed by flow cytofluorometry. Results. At the first visit and at the peak of inflammatory activity according to CRP levels and/or ESR, serum levels of sIL‐2R, IL‐6, and sTNFR in JRA patients correlated significantly with conventional inflammation indicators, whereas IL‐1β, IL‐8, and TNFα did not. No changes in leukocyte subset distribution were noted. Among the different clinical subtypes of JRA, sIL‐2R, IL‐6, and sTNFR values at the time of the initial visit showed a pattern similar to CRP, whereby patients with systemic disease exhibited by far the highest values. TNFα and IL‐1β were variably elevated in certain JRA subtypes. Patients with postinfectious arthropathies showed elevated levels of CRP, sIL‐2R, TNFα, and sTNFR, which did not differ significantly from levels in the various JRA subtypes with the exception of systemic disease. Detailed analysis of types I and II pauciarticular JRA revealed that levels of CRP, IL‐1β, and TNFα were elevated in patients with type I disease. While these parameters were invariably normal in patients with type II disease, sTNFR and sIL‐2R were still found to be significantly elevated. Followup studies suggested that persistently high sTNFR values are a better indicator of JRA activity than are measurements of other cytokines or CRP. Conclusion. JRA is associated with significant and consistent changes in serum levels of inflammatory cytokines and soluble receptors. For the clinical monitoring of JRA, determination of levels of sTNFR, and to some extent sIL‐2R, may be particularly useful, since these determinations yield information about subtype and/or activity of disease that is not available from conventional parameters of inflammation.

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Cytokines in Rheumatoid Arthritis

Cited by 76 publications

References 39 publications

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Induction of CCL13 expression in synovial fibroblasts highlights a significant role of oncostatin M in rheumatoid arthritis

Serum cytokines in juvenile rheumatoid arthritis: correlation with conventional inflammation parameters and clinical subtypes

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