Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Products of polyamine oxidation down-regulate IL-2 production by peripheral blood T cells. We show here that the production of IL-2 by rheumatoid arthritis synovial fluid mononuclear cells is inversely correlated with the concentrations of polyamines in these cells. In addition, the inhibition of polyamine biosynthesis or oxidation in cultures of these cells enhances their ability to produce IL-2. Our findings suggest that polyamine oxidation plays an important role in the suppression of T cell function characteristic of rheumatoid arthritis synovial fluids.
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PMID:Regulation of IL-2 production by mononuclear cells from rheumatoid arthritis synovial fluids. 154 27

An impermeable thiol blocker has been used to investigate the role of sulphydryl (SH) groups in the production of and responsiveness to IL-2 by normal human T lymphocytes. Surface SH blockade of mononuclear cells prior to incubation with mitogen (phytohaemagglutinin, concanavalin A, CD3 MoAb) had no effect on production of IL-2 but markedly impaired cellular responsiveness to exogenous IL-2. Studies using MoAbs indicated that this effect was accompanied by decreased expression of both the CD25 and p75 subunits of the IL-2 receptor. Blocking surface SH groups did not affect binding of IL-2 to p75 on unstimulated mononuclear cells, but inhibited binding to high-affinity receptors on a T lymphoma cell line. The data are consistent with the hypothesis that sulphydryl groups on the IL-2 receptor are required for its function and may be involved in the interaction of the CD25 and p75 subunits leading to generation of the high-affinity binding site. The surface thiol identified on the IL-2 receptor may be a candidate for oxidation on cells from patients with chronic inflammatory diseases such as rheumatoid arthritis and thus contribute to the aberrant function of T cells in these patients.
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PMID:Modulation of human T cell functions by surface sulphydryl groups: differential effects on IL-2 production and responsiveness. 156 2

Cytokines (IL-1 alpha and IL-2) and soluble interleukin 2 receptors (sIL-2r) were evaluated in patients with rheumatoid arthritis (RA) and controls. In RA, serum sIL-2r and IL-1 alpha were increased, and sIL-2r were significantly higher in synovial fluid than in serum. Serum levels of sIL-1r but not IL-1 alpha were increased in patients with acute infections, suggesting additional discriminatory specificity for IL-1 alpha. Both tender and swollen joint scores were higher for patients with RA with serum sIL-2r levels greater than or equal to 700 U/ml. Quantitation of immune mediators may be useful in the clinical assessment of RA in addition to their implication regarding the pathogenesis of the disease.
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PMID:Cytokines and soluble interleukin 2 receptors in rheumatoid arthritis. 159 71

Biologically based therapeutics may be classified as agents which (1) restore altered immunoregulatory, hematopoietic or other disease resistant functions, (2) modulate immunologic effector mechanisms (immunomodulators), or (3) upregulate or downregulate a specific cell function. There are several characteristics which differentiate biologic agents from more traditional pharmaceutical drugs. Administered parenterally, they often generate systemic effects, and may be associated with a higher placebo response. Many are administered not at pharmacologic, but "industrial strength" doses. The specific desired effect may be obscured by cytokine and other immunoregulatory networks. A host immune response typically occurs with repetitive administration; this may alter the pharmacokinetics of the agent but not necessarily the biologic or clinical effects. The use of biologic markers, both disease specific and agent specific, may allow more efficient clinical development of these agents. A variety of biologic agents are in clinical trials for the treatment of autoimmune diseases. These include interferon gamma, the IL-1 receptor antagonist and monoclonal antibodies to the T cell surface antigens CD4 and CD7. Two immunotoxins, CD5-ricin A chain, and diphtheria AB toxin-IL-2 are undergoing evaluation in rheumatoid arthritis. Data regarding these agents will be reviewed. Issues specific to their use in pediatric clinical applications will be discussed.
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PMID:The emerging role of biologics in rheumatic disease. 159

Mononuclear cells (MNC) in synovial fluids from patients with rheumatoid arthritis and other arthropathies differ clearly from MNC in peripheral blood. Typically the ratio of CD4(+)-/CD8+ lymphocytes is inverted and the response to mitogens/cytokines (IL-1/IL-2) is impaired. Active TGF-beta (transforming growth factor beta) was found to account for these abnormalities, and the major isoform was identified as TGF-beta 2.
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PMID:[Modulation of immunocompetent cells in the synovial fluid TGF-beta]. 167 45

In a previous paper (Tomura, K. et al. Tohoku J. Exp. Med., 1989, 159, 171-183), we discovered IL-2 enhancing factor(s) designated B cell derived-growth enhancing factor-2 (BGEF-2), which enhanced IL-2 dependent cell proliferation, and reported that BGEF-2 was produced by B cells of the patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) only when they were in the active stage of the disease. In this paper, we studied relationship between each IL-2 enhancing activity from B cell supernatant of the patients with these diseases and clinical parameters. IL-2 enhancing activities did not correlate with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), but correlated with plasma concentrations of gamma-globulin from the patients with RA and SLE in the active stages. IL-2 enhancing activities correlated with hypocomplementemia and leukocytopenia in the patients with SLE, and also correlated with RAHA titer in the patients with RA. Moreover, on several patients with RA or SLE in the active stages, diminution of IL-2 enhancing activity was found when they were in the remission stage after treatments. These findings suggested that IL-2 enhancing activity (i.e., BGEF-2 activity) correlated with activity of these diseases and supported the hypothesis that BGEF-2 played an important role in the polyclonal B cell activation and autoantibody production in patients with these diseases.
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PMID:Correlations between IL-2 enhancing activity and clinical parameters in patients with rheumatoid arthritis and systemic lupus erythematosus. 171 16

Eicosanoids, lymphokines, and free radicals are known to participate in the pathogenesis of inflammation. Tumour necrosis factor (TNF), interleukin-1 and 6 (IL-1 and IL-6) and colony stimulating factor -1 (CSF-1) are secreted mainly by activated macrophages, whereas T-cells secrete IL-2, IL-3, IL-4 and interferon-gamma (IFN-gamma). In addition, activated macrophages and lymphocytes can also produce eicosanoids and free radicals which have potent pro-inflammatory actions. Eicosanoids, lymphokines, and free radicals can modulate the immune response, cell proliferation, stimulate collagenase and proteases secretion and induce bone resorption; events which are known to be associated with various collagen vascular diseases. On the other hand transforming growth factor-beta (TGF-beta) produced by synovial tissue, platelets and lymphocytes can inhibit collagenase production, suppress T-cell and NK-cell proliferation and activation and block free radical generation and seems to be of benefit in rheumatoid arthritis. Drugs such as cyclosporine, 1,25,dihydroxycholecalciferol and pentoxyfylline can block lymphokine and TNF production and thus, may inhibit the inflammatory process. Essential fatty acids, the precursors of eicosanoids, are suppressors of T-cell proliferation, IL-1, IL-2 and TNF production and have been shown to be of benefit in rheumatoid arthritis, systemic lupus erythematosus and glomerulonephritis. Thus, the interactions between essential fatty acids, eicosanoids, lymphokines, TGF-beta and free radicals suggest that new therapeutic strategies can be devised to modify the course of collagen vascular diseases.
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PMID:Interaction(s) between essential fatty acids, eicosanoids, cytokines, growth factors and free radicals: relevance to new therapeutic strategies in rheumatoid arthritis and other collagen vascular diseases. 172 26

A non-radioactive in situ hybridization method for IL-2 mRNA detection based on the use of four biotinylated oligonucleotide probes, plus appropriate positive and negative control probes was developed and applied to synovial surgical and needle biopsies from rheumatoid arthritis (RA), spondyloarthropathy (SpA), psoriatic arthritis (PsA) and juvenile chronic arthritis (JCA) patients. In eight surgical biopsies (six RA, one SpA, one PsA) this non-radioactive system showed similar sensitivity to that of a previously described 32P-labelled probe system, and in addition detected IL-2 mRNA in five out of seven biopsies from SpA and PsA patients and in two out of two JCA needle biopsies. IL-2 mRNA was found in the absence of IL-2 protein in RA biopsies (six surgical, 12 needle), but variable amounts of IL-2 protein were detected in six out of seven needle biopsies from SpA, PsA and JCA patients, where CD3+ lymphoid infiltrates were present. These data suggest differences in IL-2 regulation and expression in RA and non-RA inflammatory arthropathies.
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PMID:Detection of IL-2 at mRNA and protein levels in synovial infiltrates from inflammatory arthropathies using biotinylated oligonucleotide probes in situ. 174 47

The role of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in the pathogenesis of the collagen vascular diseases was studied. The serum level of IL-4 was decreased in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD), and was variable in patients with rheumatoid arthritis (RA). The serum level of IFN-gamma was increased in patients with SLE, MCTD and RA. In patients with SLE, there was an inverse correlation between the levels of IL-4 and IFN-gamma. The proliferation and immunoglobulin production of the high-density-B cells in response to IL-4 was suppressed in normal controls, although the degree of suppression was less in patients with SLE. Cell cycle analysis using ethidium bromide demonstrated the similar findings. These data suggest that IL-4 and IFN-gamma might participate in regulating both of growth and differentiation of B cells in vivo. However, immunoglobulin production by whole B cells in response to IL-2 or PHA-induced T-cell factor was extensively facilitated by IFN-gamma in patients with SLE. It is possible that IFN-gamma enhances the differentiation of already-activated B cells, and that polyclonal B cell activation is promoted. Therefore, the failure of the regulatory mechanism by these cytokines might be related to the pathogenesis of these diseases.
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PMID:[Relationship between serum interleukin-4 or interferon-gamma level and B cell abnormality in patients with collagen vascular diseases]. 176 43

The authors assessed, using the method of sandwich enzyme immunoassay (ELISA), the soluble receptor for interleukin-2 (s-r IL-2). In patients with rheumatoid arthritis mean values of 620.5 = 500.0 u./ml were recorded which was significantly higher than in patients with osteoarthritis (p less than 0.001) (313.3 +/- 155 n./ml) and in healthy controls (181.7 +/- 159.6 n./ml). In patients with rheumatoid arthritis a correlation was found between the activity of the disease expressed by means of Lansbury's index (r = 0.61, p less than 0.01). There was no correlation between s-r IL-2 and the sedimentation rate (r = 0.32, p = n.s.). The author reviews the literature and discusses the hypothesis that s-r IL-2 acts as a competitive inhibitor for interleukin-2.
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PMID:Levels of the soluble receptor for interleukin-2 in serum of patients with rheumatoid arthritis. 180 34


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