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)

Because previous studies showed low levels of IFN-gamma in rheumatoid arthritis (RA) synovial fluid (SF) and synovial tissue (ST) explant supernatants, we assayed RA SF and ST for IL-2 and IL-3-like activity. Using an IL-2 dependent murine CTLL line, 6 of 14 RA SF caused increased thymidine uptake (greater than three times control). The activity was distinct from IL-2 because it was not blocked by antibody to IL-2-R. In addition, IL-2 was not detected (less than 50 pg/ml) in 16 joint samples using an ELISA. Multi-colony-stimulating factor (CSF) activity was measured using two assays that can detect murine IL-3 (mast cell proliferation, and bone marrow CSF). In the mast cell assay, [3H]TdR uptake was 493 +/- 67 cpm for medium, 2,910 +/- 329 cpm in the presence of RA SF (p less than 0.001), 1,246 +/- 156 cpm in the presence of SF from patients with seronegative spondyloarthropathies (p less than 0.001), and 736 +/- 100 cpm in the presence of osteoarthritis SF (p greater than 0.1). In the CSF assay, four of five RA SF and five of five RA ST induced colony formation from bone marrow nonadherent cells. Macrophage colonies were most common, although mixed colonies and granulocytes were occasionally observed. The multi-CSF activity in RA is not due to IL-3 since human rIL-3 was not active in either murine assay, and IL-3 mRNA was not detected in RA synovium. Sephadex column chromatography of RA SF revealed that the mast cell growth factor (approximately 6 x 10(3) mol wt) and the CSF (approximately 40 and 100 x 10(3) mol wt) are distinct. The colony-stimulating aspect of the "IL-3-like" activity in RA SF is likely due to CSF-1 because it is the appropriate mol wt and because the activity was neutralized by specific anti-CSF-1 antibody. Finally, an RIA detected 1.6-25 ng/ml of CSF-1 in RA SF and ST and CSF-1 mRNA was detected in four of five RA synovial tissue samples tested.
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PMID:Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. 326 64

T cells spontaneously responsive to interleukin (IL)-2 were cloned from the peripheral blood (PBL) or synovial fluid (SFL) lymphocyte populations obtained from patients with rheumatoid arthritis (RA) or from normal PBL. The clones were compared for their capacities to produce fibroblast-activating factors (FAFs) which support the growth of RA synovial fibroblasts. Clones derived from all sources produced FAFs following mitogen stimulation, but SFL clones synthesized significantly higher levels of FAF activity. Physicochemical characterization of the FAFs suggested that SFL- and PBL-derived clones produced similar factors. It was also demonstrated that interferon-gamma and IL-2 did not contribute to the FAF activity of the clone supernatants. These results demonstrate that a subpopulation of activated lymphocytes which are present in increased numbers in the rheumatoid joint can produce factors which influence rheumatoid synovial cell growth.
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PMID:Fibroblast-activating factor production by interleukin (IL)-2 dependent T-cell clones from rheumatoid arthritis patients and normal donors. 326 57

The lymphokine-activated killer (LAK) cell activity in the peripheral blood of 23 patients with rheumatoid arthritis has been studied. Two control groups comprised (a) nine patients with another chronic inflammatory disease (sarcoidosis) and (b) 19 normal healthy volunteers. The LAK activity induced by human recombinant IL-2 was very similar in controls and patients with rheumatoid arthritis but was significantly decreased in patients with sarcoidosis, although the frequency of LAK-cell precursors measured using a limiting dilution assay was comparable in all three groups. The DNA synthetic response of peripheral blood mononuclear (PBM) cells to IL-2 was slightly decreased in patients with both rheumatoid arthritis and sarcoidosis as compared to controls, but this decrease was not statistically significant. Spontaneous DNA synthesis in PBM cells cultured in the absence of IL-2 was essentially identical in all three groups. We conclude on the basis of these results that the higher risk of non-Hodgkin's lymphomas in patients with rheumatoid arthritis cannot be attributed to an impairment of LAK activity. Furthermore, the doses of gamma-irradiation, which abolished the 'background' cytotoxicity of PBM cells cultured without IL-2 and also blocked effectively both spontaneous and exogenous IL-2-dependent DNA synthesis, had little effect on the generation of LAK activity. These observations are discussed in regard to the role of non-specific cytotoxic cells and the therapeutic efficacy of antiproliferative drugs in rheumatoid arthritis.
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PMID:Lymphokine-activated killer cell activity in rheumatoid arthritis. 349 78

Lymphocytes from peripheral blood (PBL) and synovial fluid (SFL) were obtained from patients with rheumatoid arthritis (RA) and cloned under limiting-dilution conditions without prior activation but in the presence of exogenous interleukin (IL)-2. The precursor frequencies of such in vivo activated IL-2-responsive cells were higher in RA SFL (1/83) than in RA PBL (1/201) or normal PBL (1/377). These HLA-Dr/Ia-positive clones expressed T-cell markers CD3 and T101 and were either CD4- or CD8-positive but lacked NK markers CD11, CD16, and HNK-1. All such clones were cytotoxic for NK-sensitive K562 targets and NK-insensitive Raji cell targets. These cells, which most closely resemble nonmajor histocompatibility complex (MHC) restricted cytotoxic T (CTL) cells, are present with increased frequency in RA synovial fluids.
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PMID:Characterization of IL-2 responsive synovial T lymphocytes in rheumatoid arthritis. II. Functional properties. 349 51

Isoprinosine (IPS) is a new anti-viral agent which appears to have immunomodulatory activities which include its ability to enhance the in vitro blastogenic responses of normal lymphocytes to mitogens. The present study compares the effects of IPS on the in vitro immune functions of peripheral blood mononuclear cells (PBMC) from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients with its effects on PBMC from normal controls. Each mitogen (Con A, PHA or PWM) was used at its optimal concentration with a range of IPS concentrations (0-25 micrograms/ml). PHA-induced blastogenesis by PBMC from all three groups was enhanced by IPS at or above 5 micrograms/ml. The Con A-induced responses of SLE lymphocytes were significantly enhanced over controls by IPS (P less than 0.02 at 5 micrograms/ml) while those of RA lymphocytes were not. IPS had little effect on PWM-induced blastogenesis by RA lymphocytes but did enhance the blastogenic responses of SLE lymphocytes (P less than 0.01 at 5 micrograms/ml). In contrast, the characteristically high immunoglobulin synthesis by SLE lymphocytes was decreased by IPS. The mechanism responsible for these effects is not known but IL-2 production by patient lymphocytes in vitro which was low for both RA (P less than 0.01) and SLE (P less than 0.02) increased significantly (P less than 0.05) when SLE lymphocytes were cultured with IPS. These data identify IPS as an agent for the study of aberrant immune regulation in autoimmune diseases and suggest that it may have potential therapeutic value in SLE.
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PMID:Immunomodulation by isoprinosine: effects on in vitro immune functions of lymphocytes from humans with autoimmune diseases. 619 May 98

We have previously demonstrated defective antigen specific T-suppressor (Ts) cell function in the peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA). Our study was designed to delineate whether diminished Ts activity is due to impaired interleukin (IL) dependent clonal expansion of Ts cells or to prior in vivo activation. Patients with recent onset of RA, or a disease flare, exhibited enhanced IL generation (IL-1 and /or IL-2). Increased proportions of active E-rosettes, elevated spontaneous production of IgM, and total immunoglobulin in mitogen free cultures were consistent with the concept of prior lymphocyte activation in vivo. Our results do not support defective clonal expansion of Ts cells as the basis of deficient IL generation, but do support the concept of in vivo activation of PBM cells in some patients with RA.
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PMID:Evidence for activated peripheral blood T-cells in rheumatoid arthritis. 623 Apr 49

Synovial fluids from rheumatoid arthritis (RA) patients were found to contain activated T lymphocytes that could be maintained as continuous T cell lines (CTCL) in the presence of the T cell growth factor, interleukin (IL)-2. The CTCL predominantly expressed the OKT8 phenotype and were Ia antigen positive. IL-2-dependent RA CTCL could be maintained in an active dividing state by the presence of RA synovial fluids, whereas IL-2-dependent CTCL from mitogen stimulated PBL failed to respond to the fluids, which were shown to contain IL-2. This suggested that RA CTCL exhibit unique properties not possessed by normal PBL CTCL. The CTCL generated from activated synovial T lymphocyte populations in RA may be used to assess the functions of these cells and their responses to regulatory factors.
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PMID:Generation of interleukin-2-dependent T cell lines from synovial fluids in rheumatoid arthritis. 633 90

Lewis rats injected in the hind paw with Mycobacterium butyricum develop a severe polyarthritis which shares certain features in common with rheumatoid arthritis in man. Spleen and peripheral blood mononuclear cells from rats with this form of arthritic disease proliferate poorly in vitro in response to concanavalin A (con A), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM). The splenic hyporesponsiveness appears within four days of M. butyricum injection (three to five days prior to the development of detectable arthritis), reaches a peak 16-22 days following injection, and persists for at least 40 days. Buffalo strain rats injected with M. butyricum do not develop arthritis, and their spleen cells respond normally to con A, PHA, and PWM. In response to lipopolysaccharide (LPS) the synthesis of interleukin 1 (IL-1) by spleen or peritoneal macrophages from arthritic Lewis rats equalled or exceeded that of macrophages from normal rats. In contrast splenic T cells from arthritic rats produced reduced amounts of interleukin 2 (IL-2; T cell growth factor) in response to stimulation with PHA or con A. Moreover, con-A-activated spleen cells from arthritic rats failed to bind IL-2 and to respond to this growth factor with increased 3H-TdR uptake as did normal spleen cells. In-vitro treatment of 'arthritic' cells with 10(-5) M indomethacin did not restore to normal their reduced mitogen responsiveness, and spleen cells from normal and arthritic rats were equally sensitive to the inhibitory effects of prostaglandin E2 on con-A-induced proliferative responses. These results indicate that peripheral lymphoid function is compromised in rats with adjuvant-induced arthritis and that this functional deficit is mediated by aberrant synthesis of and response to IL-2 by T cells of arthritic animals.
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PMID:Lymphoid abnormalities in rats with adjuvant-induced arthritis. I. Mitogen responsiveness and lymphokine synthesis. 633 88

Using lectin-free IL-2 as the only initial stimulus, bulk cultures and T-cell clones were established from synovial fluid (SFL) and peripheral blood lymphocytes (PBL) of a patient with rheumatoid arthritis (RA). The cloning efficiency of growing bulk cultures was 3%-4% as evaluated by Poisson statistics and was not enhanced by the addition of autologous synovial fluid or serum. The majority of the cloned T cells expressed the OKT8+ phenotype; several clones were OKT4+ and one clone expressed OKT8+ and OKT4+ antigens. None of the cloned T cells exhibited high NK or lectin-dependent cytotoxicity, although bulk cultures had high NK activity. In primed lymphocyte typing responses, bulk cultures and two T-cell clones established from rheumatoid SFL and PBL showed consistent autoreactivity, which we have never before observed with MLC-derived bulk cultures and T cell clones. One of the autoreactive rheumatoid T-cell clones (B25) was found to provide strong helper activity to autologous B cells in the absence of mitogen. Attempts to reveal reactivity of RA-derived T-cell clones to microbial antigens have so far only been successful with Mycoplasma pneumoniae preparations. Careful analysis of this reactivity revealed, however, that Mycoplasma pneumoniae induces a stimulator cell-dependent mitogenic effect rather than an antigen-specific MHC-restricted T-cell proliferation.
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PMID:Analysis of T-cell cultures and clones from a patient with classic rheumatoid arthritis--evidence for the existence of autoreactive T-cell clones in blood and synovial fluid. 633 24

The depressed cell-mediated immunity in rheumatoid arthritis was investigated in vivo by cutaneous hypersensitivity responses to seven antigens including tuberculin PPD, and in vitro by lymphocyte transformation to the latter antigen. In vivo 40% of rheumatoid patients were anergic compared to 2% of controls (P less than 0.001) with an associated reduction in sum score (5.9 +/- 6.5 vs 15.3 +/- 8.7, P less than 0.001). In vitro lymphocyte proliferation to PPD was also significantly depressed (P less than 0.001) and could not be reversed by indomethacin. A significant correlation between the in vivo sum scored (induration in mm) and in vitro thymidine incorporation (d/min) (r = 0.59, P less than 0.001) was found. In an attempt to overcome the depressed in vitro response the addition of a crude supernatant from a mixed lymphocyte reaction was found to return the PPD stimulated lymphocyte proliferation to the normal range. This effect was mimicked by purified IL-2 but not purified IL-1. The implications of this finding are are discussed.
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PMID:Interleukin-2 reverses deficient cell-mediated immune responses in rheumatoid arthritis. 661 Dec 30


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