Circulating soluble tumor necrosis factor receptors, interleukin‐2 receptors, tumor necrosis factor α, and interleukin‐6 levels in rheumatoid arthritis.

Barrera, Pilar; Boerbooms, A. M. T.; Janssen, Elly M.; Sauerwein, Robert W.; Gallati, H.; Mulder, Jan De; Boo, Theo de; Demacker, P.N.M.; Putte, L. B. A. Van De; Meer, J.W.M. van der

doi:10.1002/art.1780360807

Cited by 131 publications

(58 citation statements)

References 38 publications

(33 reference statements)

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“…Limited information exists concerning the effect of MTX on TNF-a. However, reduced secretion of soluble TNF receptor was shown in RA patients following MTX treatment [18].…”

Section: Discussionmentioning

confidence: 99%

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Methotrexate treatment in murine experimental systemic lupus erythematosus (SLE); clinical benefits associated with cytokine manipulation

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Dayan

Zinger

et al. 1995

Clinical and Experimental Immunology

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SUMMARY The objective of this study was to determine the effects of Methotrexate (MTX) on the development and the course of experimental murine SLE, as well as on the cytokine profile involved in the disease. SLE was induced in naive BALB/c female mice by injection of the human anti‐DNA MoAb bearing a common idiotype (16/6 Id). Six weeks following immunization, when high levels of autoantibodies were demonstrated, the mice were treated with MTX (2 mg/kg once a week) for a period of 10 months. MTX treatment had no effect on 16/6 Id‐induced autoantibody production. However, MTX treatment had beneficial effects on the clinical manifestations of the experimental disease (i.e. leucocyte counts, levels of protein in the urine and immune complex deposits in the kidneys). Thus, only 20% of 16/6 Id‐immunized BALB/c mice that were treated with MTX had immune complex deposits in their kidneys compared with 100% of SLE‐afflicted BALB/c mice that were not treated. We have observed a significant elevation in IL‐1, tumour necrosis factor (TNF) and IL‐10 secretion in BALB/c mice afflicted with experimental SLE. IL‐2, IL‐4, IL‐6 and interferon‐gamma (INF‐γ) levels were decreased in these mice compared with the levels detected in healthy controls. Treatment with MTX reversed the levels of all the above cytokines to normal levels observed in control mice. These studies demonstrate therapeutic effects of MTX on murine experimental SLE. The normal cytokine profile observed following treatment with MTX is suggested to play a role in the amelioration of the clinical manifestations of experimental SLE.

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“…Limited information exists concerning the effect of MTX on TNF-a. However, reduced secretion of soluble TNF receptor was shown in RA patients following MTX treatment [18].…”

Section: Discussionmentioning

confidence: 99%

“…Further. MTX was shown to cause a decrease in IL-6 activity [17,18] and IL-8 activity [19], MTX has also been shown to lower soluble TNF receptor and IL-2 receptor levels [18,20].…”

mentioning

confidence: 99%

Methotrexate treatment in murine experimental systemic lupus erythematosus (SLE); clinical benefits associated with cytokine manipulation

Segal

Dayan

Zinger

et al. 1995

Clinical and Experimental Immunology

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“…In RA, soluble forms of Fcy receptor 111, IL-2 receptor a chain, intercellular adhesion molecule 3, and TNF receptor have been detected in sera or synovial fluid (22)(23)(24)(25)(26)(27)(28). Among these, the serum level of p55 soluble TNF receptor has been reported to be useful in the evaluation of RA disease activity and of treatment efficacy (27,28). Since the expression of BST-1 is enhanced on RA-derived bone marrow stroma1 cell lines compared with healthy donor-derived lines and BST-1 seems to play a role in B lymphopoiesis as well as to affect various activities of a variety of cells, BST-1 may be involved in the pathogenesis of RA.…”

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confidence: 99%

Elevated levels of the soluble form of bone marrow stromal cell antigen 1 in the sera of patients with severe rheumatoid arthritis

Lee

Ishihara

et al. 1996

Arthritis & Rheumatism

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Objective. Bone marrow stromal cell antigen 1 (BST‐1) is a novel glycosyl phosphatidylinositol–anchored ectoenzyme, which is overexpressed on bone marrow stromal and synovial cell lines derived from patients with rheumatoid arthritis (RA). To investigate the pathophysiologic roles of BST‐1 in RA, we established an enzyme‐linked immunosorbent assay (ELISA) system to detect the soluble form of BST‐1 (sBST‐1) and examined levels of sBST‐1 in the sera of RA patients. Methods. Concentrations of sBST‐1 in sera from healthy donors and from patients with RA, osteoarthritis, Sjögren's syndrome, and systemic lupus erythematosus were measured with the ELISA. Results. In 7% of the RA patient samples (10 of 143), concentrations of serum sBST‐1 were higher (∼30–50‐fold) than in non‐RA samples. Serum sBST‐1 concentrations showed no correlation with age, C‐reactive protein level, or rheumatoid factor level. All RA patients with high concentrations of serum sBST‐1 had severe disease with involvement of several large joints. Conclusion. We believe the measurement of serum sBST‐1 may have prognostic value, but further analysis is necessary to clarify the clinical significance of elevated sBST‐1 in RA.

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“…The IL-1 receptor antagonist (IL-1RA), a competitive inhibitor of IL-1 which binds to the IL-1 receptors without inducing a biological response [16] is present in the rheumatoid synovial membrane [17]. High concentrations of soluble recep tors for IL-2 (sIL-2R) [18][19][20] and TNF (sTNFR) [19,21] have been detected in plasma and synovial fluid of RA patients. The sIL-2R, a soluble form of the a chain IL-2 receptor, is a marker of lymphocyte activation in vivo [22] and may be useful to monitor disease activity in RA [18].…”

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confidence: 99%

Effect of Methotrexate Alone or in Combination With Sulphasalazine on the Production and Circulating Concentrations of Cytokines and Their Antagonists. Longitudinal Evaluation in Patients With Rheumatoid Arthritis

et al. 1995

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S U M M A R YIn a recent study from our group, the combination of methotrexate and sulphasalazine (MTX + SASP) seemed superior to MTX alone in the treatment of rheumatoid arthritis (RA). To assess the impact of these therapies on the cytokine cascade, the in vitro production and circulating concentrations of several cytokines and endogenous cytokine antagonists were measured in 30 healthy controls and longitudinally in a subset of 26 patients enrolled in this study. Compared to controls, RA patients had significantly higher circulating concentrations of interleukin-6 (IL-6), soluble receptors for tumour necrosis factor (sTNFR), soluble receptors for interleukin-2 (sIL-2R) and interleukin-1 receptor antagonists (IL-1RA), and their peripheral blood mononuclear cells (PBMNC) showed a higher spontaneous production of interleukin-1/i (IL-l/i), tumour necrosis factor a (TNFa) and IL-1RA (both secreted and cell-associated) and a higher stimulated production of cell-associated TNFa, IL-1RA and (to a lesser extent) IL-l/i. Treatment with MTX alone (n = 12) or combined with SASP (n = 14), resulted in significant reductions of circulating IL -6 and sIL-2R but did not alter IL-l/i, TNFa or IL-1RA concentrations. Decreases in circulating levels of sTNFR and in the in vitro production of cell-associated IL-l/i and IL-1RA after stimulation were only observed in patients treated with MTX + SASP. The concentrations of IL-1RA and sTNFR in the circulation exceeded moderately those of IL-l/i and TNFa but this is probably insufficient to block IL-1 and TNFa activity. In conclusion, therapy with MTX alone or with SASP modulates IL -6 and sIL-2R concentrations in RA. Decreased production of IL-l/i and IL-1RA and circulating sTNFR levels were only observed during therapy with MTX -f SASP. Whether this relates to the better clinical effect observed with the combination therapy remains to be investigated. Circulating levels of IL-6, sIL-2R and sTNFR seem useful markers of disease activity in RA.K ey w o r d s : Cytokines, Methotrexate, Sulphasalazine, Combination therapy.

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Circulating soluble tumor necrosis factor receptors, interleukin‐2 receptors, tumor necrosis factor α, and interleukin‐6 levels in rheumatoid arthritis.

Cited by 131 publications

References 38 publications

Methotrexate treatment in murine experimental systemic lupus erythematosus (SLE); clinical benefits associated with cytokine manipulation

Methotrexate treatment in murine experimental systemic lupus erythematosus (SLE); clinical benefits associated with cytokine manipulation

Elevated levels of the soluble form of bone marrow stromal cell antigen 1 in the sera of patients with severe rheumatoid arthritis

Effect of Methotrexate Alone or in Combination With Sulphasalazine on the Production and Circulating Concentrations of Cytokines and Their Antagonists. Longitudinal Evaluation in Patients With Rheumatoid Arthritis

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