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)

Interleukin 1 beta (IL-1 beta) is a polypeptide with pro-inflammatory and immunopotentiating effects in vivo and in vitro. With relevance to rheumatoid arthritis (RA) IL-1 augments release of prostanoids, proteinases and oxygen metabolites and is a potent inducer of bone and cartilage resorption. Although high levels of IL-1 have been found in rheumatoid synovial fluids, intra-individual variation in IL-1 production has made it difficult to correlate these levels with disease activity. To overcome this problem we have studied patients with symmetrical and asymmetrical knee joint inflammation. Local disease activity was documented using Ritchie score and joint circumference; IL-1 beta levels were quantitated in synovial fluid by ELISA. In patients with symmetrical joint involvement almost identical levels of IL-1 beta were detected in the right and left knee joints. In contrast, in patients exhibiting asymmetrical knee joint involvement, IL-1 beta levels in the inflamed joints were significantly higher than in the contralateral joints. The study provides further evidence for the role of IL-1 in the pathogenesis of rheumatoid inflammation.
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PMID:Interleukin 1 beta in synovial fluid is related to local disease activity in rheumatoid arthritis. 207 74

Twenty-four patients with rheumatoid arthritis (RA) and 20 normal controls were examined for the ability of their peripheral blood B cells to produce interleukin 1 (IL-1) with or without lipopolysaccharide (LPS). B cells were purified from peripheral blood by negative selection methods (i.e., removal of adherent cells and sheep red blood cell rosette-forming cells, followed by treatment with monoclonal antibodies (OKT3 and OKM1) and complement). The amount of IL-1 in B cell culture supernatants (SN) was measured by thymocyte and fibroblast proliferation assays and an enzyme-linked immunosorbent assay for IL-1 alpha and beta. As a group, cultured B cells from patients with RA, both spontaneously and when stimulated with LPS, produced higher levels of IL-1 than those from normal controls. IL-1 production by RA B cells with LPS had a weak but positive correlation with disease activity. Moreover, RA B cell culture SN with elevated levels of IL-1 had a synergistic effect on the growth of anti-human IgM (anti-mu) stimulated B cells. In separate experiments, the growth of RA B cells was significantly promoted by IL-1 beta both with and without anti-mu stimulation. These results suggest that B cell-derived IL-1 may be involved in the B cell clonal expansion of RA through its own activity as a B cell stimulatory factor.
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PMID:Increased ability of peripheral blood B cells from patients with rheumatoid arthritis to produce interleukin 1 in vitro. 207 29

Cartilage breakdown in rheumatoid arthritis results from (a) lytic action by synovial enzymes, and (b) release of synovial catabolin, now believed to be a form of interleukin 1 (IL-1), causing chondrocytes to degrade their matrix. Rheumatoid synovial culture media were tested for their ability to stimulate cartilage degradation (proteoglycan release from bovine nasal cartilage discs) and thymocyte proliferation (3H-thymidine incorporation) in the absence or presence of anti-IL-1. Degradation of living cartilage, stimulated 2-fold by synovial culture media, was inhibited up to 80% by anti-IL-1. Residual breakdown in living cartilage and synovial culture media induced breakdown in dead cultures were of similar magnitude, and both were unaffected by antibody treatment. Proteoglycan products released from synovial culture media treated cartilage were of smaller average molecular weight (Sepharose CL-2B), and such size reduction was inhibited by anti-IL-1 treatment. Synovial culture media that stimulated cartilage degradation also stimulated thymocyte proliferation; the latter was fully suppressible by anti-IL-1. One of 8 synovial culture media contained an inhibitor(s) of thymocyte proliferation, removable by dialysis. We conclude (1) rheumatoid synovial catabolin activity is due to a form of IL-1. (2) A minor nonsuppressible component of synovial culture media stimulated breakdown, identical in living and killed cartilage, is due to passive transfer of enzymic activity. (3) Cultured rheumatoid synovium releases both IL-1 and an inhibitor(s) of IL-1 action.
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PMID:Antibody to interleukin 1 inhibits the cartilage degradative and thymocyte proliferative actions of rheumatoid synovial culture medium. 208 32

Previous studies of the cytokine profile of rheumatoid arthritis (RA) have been primarily limited to the assessment of the levels of these mediators in synovial fluid (SF) or synovial tissues (ST) by biologic or immunologic assays. We have studied cytokine gene expression in RA by in situ hybridization of SF cells, enzymatically dispersed ST cells, and frozen sections of ST. RA ST cells (n = 7) were studied and a high percentage of cells hybridized to the following anti-sense probes: IL-6 = 19 +/- 3.3%; IL-1 beta = 9.9 +/- 1.7%; TNF-alpha = 5.8 +/- 1.4%; granulocyte-macrophage-CSF = 2.2 +/- 0.8%; transforming growth factor-beta 1 = 1.3 +/- 0.2% (p less than 0.05 for each compared to sense probes). Similar results were found using osteoarthritis ST cells, although the percentage of cells expressing the IL-6 gene (7.1 +/- 2.5%) was significantly less in osteoarthritis compared to RA. RA ST cells did not significantly bind the IFN-gamma probe (0.2 +/- 0.1% positive), although they were capable of expressing the IFN-gamma gene if stimulated with PHA. The OKM1+ population of ST cells (i.e., macrophage lineage cells) was greatly enriched for IL-1 beta and TNF-alpha, whereas the OKM1- population (lymphocytes, fibroblasts, and type B synoviocytes) was enriched for IL-6. The vast majority of cells expressing the IL-6 gene were non-T cells. Furthermore, hybridization to RA ST frozen sections localized IL-6 mRNA to the synovial lining layer, which is comprised of type A and type B synoviocytes. In contrast to the high level of cytokine gene expression observed in ST, SF cells did not hybridize significantly to any of the cytokine probes. If stimulated with LPS or PHA, SF cells expressed IL-1 beta or IFN-gamma genes, respectively.
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PMID:Quantitative analysis of cytokine gene expression in rheumatoid arthritis. 210 76

A decreased production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) upon in vitro stimulation by phytohemagglutinin (PHA) peripheral blood leucocyte in active rheumatoid arthritis (RA) patients has been described as an important immunological abnormality in this disease. However, the molecular level at which this defect might occur has not been fully documented. We have investigated the kinetics of IFN-gamma, interleukin-2 receptor (IL-2 R), and interleukin-1 beta (IL-1 beta) messenger RNA (mRNA) expression in RA patients (n = 9) and normal controls (n = 5) after PHA leucocyte activation. We demonstrate here a significantly decreased expression of IFN-gamma mRNA in RA patients without modification of its kinetics associated with a similar IL-1 beta mRNA expression.
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PMID:Interferon-gamma mRNA expression upon in vitro T lymphocyte activation is decreased in rheumatoid arthritis patients. 211 47

The production of collagen and glycosaminoglycans (GAG) was studied in cultured human synovial cells exposed to four cytokines, alone or in dual combination, namely interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta). Among these cytokines, only TGF-beta (0.1-10 ng/ml) induced a significant and dose-dependent increase of collagen synthesis in a 24-h incubation. This effect was reversed when the factor was associated with either IL-1 beta (100-500 pg/ml), TNF-alpha (1-100 ng/ml) or IFN-gamma (100 U/ml). Except IFN-gamma which clearly inhibits the collagen production, the other cytokines IL-1 and TNF-alpha were not very effective when tested separately, although they generally induced a small reduction in collagen amount. IL-1 beta and TNF-alpha were found to be more efficient than TGF-beta in stimulating the production of GAG by the synovial cells. IFN-gamma exerted an antagonistic effect on the TGF-beta-induced stimulation of GAG synthesis. TNF-alpha and IL-1 beta were shown to have an additive effect on that production. The results indicate that interactions between cytokines present in the inflamed synovial tissue may modulate their respective actions and thus introduce differentials in their effect on collagen and GAG metabolism which are responsible for the alterations of synovial extracellular matrix in rheumatoid arthritis.
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PMID:Effects of associated cytokines (IL-1, TNF-alpha, IFN-gamma and TGF-beta) on collagen and glycosaminoglycan production by cultured human synovial cells. 211

We studied the role of T cells in the production of osteoclast activating factor (OAF) using anti-CD3 MAb as a specific T cell activator. OAF activity was totally inhibited by anti-IL-1 beta. Peripheral blood mononuclear cells (PBMNC) from normal subjects produced more OAF than did PBMNC from rheumatoid arthritis (RA) patients. Mononuclear cells (MNC) from RA synovial fluid produced less OAF than did RA peripheral blood. We conclude that (i) specific T cell stimulation induces OAF production which may be attributed to interleukin 1 (IL-1) activity, (ii) the inhibition by anti-IL-1 beta of OAF production following anti-CD3 stimulation suggests that the T cell signal is being transmitted to the macrophage, and (iii) RA MNC are deficient in T cell-mediated OAF production.
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PMID:Induction of bone resorbing activity by normal and rheumatoid arthritis T cells. 214 27

Cultures of human rheumatoid synovial cells and rabbit articular chondrocytes were exposed to various concentrations of Etodolac (from 0.01 to 10 micrograms/ml) in presence or absence of 500 pg/ml (5 U/ml) human recombinant Interleukin-1 beta (IL-1 beta). Incubation of chondrocytes with Etodolac for 24 h did not alter collagen biosynthesis. In contrast, 1 micrograms/ml Etodolac caused a 20% increase of collagen production in synoviocytes. Addition of Etodolac in combination with IL-1 could partially suppress the inhibitory effect exerted by the cytokine on both cell types. Four-day exposure of chondrocytes to 0.1 and 1 micrograms/ml Etodolac led to an increased accumulation of collagen in the cell layer compartment. However, this treatment could not prevent the inhibitory effect of IL-1 on this collagen fraction. Treatment of synoviocytes for eight days with the same concentrations of Etodolac did not modify their collagen production but suppressed totally the inhibitory effect of IL-1. These data show that Etodolac is able to augment chondrocyte metabolism during a long term treatment. Moreover, under certain conditions, this drug can reduce or even suppress the IL-1-induced inhibition of collagen biosynthesis, a process that may take a part in the connective tissue alterations associated with osteoarticular diseases such as rheumatoid arthritis and osteoarthritis.
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PMID:Modulation of extracellular matrix metabolism in rabbit articular chondrocytes and human rheumatoid synovial cells by the non-steroidal anti-inflammatory drug etodolac. I: Collagen synthesis. 215 Jul 40

Monocytes from peripheral blood and synovial fluid of patients with definite and classic rheumatoid arthritis spontaneously produced significantly greater amounts of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and interleukin-1 beta (IL-1 beta) than samples of peripheral blood from normal controls. Peripheral blood monocytes from patients with rheumatoid arthritis produced significantly greater amounts of PGE2 than control samples when stimulated with lipopolysaccharide. There were no significant differences in the spontaneous release of superoxide or N-acetyl-beta-D-glucosaminidase by peripheral blood monocytes between patients and healthy controls. Both stimulated and unstimulated peripheral blood monocytes from patients with definite or classic rheumatoid arthritis produced significantly greater amounts of PGE2 than samples from normal controls. This was true, regardless of the stage of disease and the presence or absence of roentgenological joint abnormalities. Amounts of N-acetyl-beta-D-glucosaminidase released by peripheral blood monocytes from patients correlated positively with the erythrocyte sedimentation rate (ESR) and negatively with duration of disease. Amounts of IL-1 beta and N-acetyl-beta-D-glucosaminidase released from the peripheral blood monocytes of patients who had had their disease for less than one year were significantly higher than those of normal controls. There were no significant correlations between the types of treatment and the amounts of PGE2, LTB4, IL-1 beta or N-acetyl-beta-D-glucosaminidase released by peripheral blood monocytes in patients with rheumatoid arthritis. The findings suggest that monocytes are activated in patients with rheumatoid arthritis both at the onset of disease and during its chronic phase, and that they produce large amounts of mediators which may have a role in the induction and extension of the inflammatory process which leads to tissue damage.
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PMID:Monocyte activation in early onset rheumatoid arthritis. 216 87

The growth of adherent synovial cells passaged once was studied in response to human recombinant interleukin 1 (hr IL-1) beta. Human synovial cell cultures were established from tissues obtained during therapeutic joint surgery for patients with rheumatoid arthritis (rheumatoid synovial cells, RSC) or non inflammatory rheumatic diseases (non rheumatoid synovial cells, NRSC). The effect of IL-1 beta (0.1 to 10 ng/ml) on the time course of proliferation showed that values for DNA synthesis and cell numbers in RSC cultures were higher than in NRSC cultures. Similarly, untreated control RSC cultures grew more quickly than NRSC. These results demonstrate that RSC, which are continuously stimulated by IL-1 beta produced in the rheumatoid pannus in vivo, have a higher capacity for proliferation than NRSC but are less responsive to IL-1 beta. A dose-response curve of proliferation was established 72 hrs. after the addition of IL-1 to the medium. The stimulating effect of IL-1 beta (0.001 to 10 ng/ml) was dose-dependent in both RSC and NRSC and reached a plateau at 10 ng/ml; the response of NRSC was stronger than that of RCS.
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PMID:Effects of human recombinant IL-1 beta on rheumatoid and non rheumatoid human synovial cell growth. 222 55


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