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)

We report the use of granulocyte-macrophage colony stimulating factor (GM-CSF) in a case of rheumatoid arthritis with sulfasalazine induced agranulocytosis, leading to a rapid bone marrow recovery within 7 days. This case and 2 others reported in the literature emphasize the need for further research into the possible role of GM-CSF in the treatment of drug induced agranulocytosis.
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PMID:Sulfasalazine induced agranulocytosis treated with granulocyte-macrophage colony stimulating factor. 135 Jun 40

The effect of auranofin on granule protein secretion from neutrophils was investigated by a haemolytic plaque assay which can detect release of lactoferrin and myeloperoxidase from single adherent neutrophils. Lactoferrin secretion in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) was enhanced at low (0.25-1.0 micrograms/ml) and inhibited at high concentrations of auranofin (50% inhibition (IC50) at 3.7 micrograms/ml). A similar biphasic effect was also seen on degranulation mediated by granulocyte-macrophage colony stimulating factor (GM-CSF) (IC50 1.8 micrograms/ml). In contrast, exocytosis mediated by tumour necrosis factor was inhibited even at low concentrations of auranofin (IC50 0.6 micrograms/ml). Secretion induced by phorbol 12-myristate 13-acetate and A23187 was only inhibited at very high auranofin concentrations (IC50 10 and 8 micrograms/ml respectively). The effect of auranofin on myeloperoxidase secretion was also assessed and the IC50 values for the respective agents were as follows: tumour necrosis factor 0.7 micrograms/ml, fMLP 1.6 micrograms/ml, and phorbol myristate acetate 7.6 micrograms/ml. When neutrophils were preincubated with auranofin (4 micrograms/ml) and then exposed to fMLP, tumour necrosis factor, or GM-CSF in the absence of auranofin, lactoferrin release was enhanced if the preincubation time was short (one to three minutes) and inhibited when the time of preincubation was longer. It was concluded that auranofin, at concentrations achieved in the serum of patients, is a potent inhibitor of cytokine induced release of granule proteins from adherent neutrophils. This finding may be of clinical importance and shed light on the mechanism by which auranofin acts in rheumatoid arthritis.
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PMID:Effect of auranofin on cytokine induced secretion of granule proteins from adherent human neutrophils in vitro. 164 54

A number of fibroblastoid synovial cell lines have been established from rheumatoid joints. These cell lines were shown to express the interleukin 6 (IL-6) gene constitutively, and exposure of these cells to 5 ng/ml of recombinant human interleukin 1 beta (IL-1 beta) increased IL-6 gene expression. Other recombinant human lymphokines, namely interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony stimulating factor had no enhancing effect on IL-6 gene expression. Dexamethasone added to the cultures at 10(-7) M concentration suppressed the constitutive expression of the IL-6 gene. At a concentration of 10(-5) M, dexamethasone partially suppressed the IL-1 enhanced expression of IL-6. The IL-6 gene probe also hybridized to RNA from unfractionated synovial fluid cells, peripheral blood T cells and non-T cells but not Epstein-Barr virus transformed peripheral blood B cells of patients with rheumatoid arthritis. Our results suggest that in rheumatoid arthritis, synovial fibroblasts actively participate in joint inflammation by lymphokine production. The coexpression of both IL-1 and IL-6 by one synovial fibroblast line suggests a mechanism for the perpetuation of synovitis.
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PMID:Expression of the interleukin 6 gene in rheumatoid synovial fibroblasts. 170 61

The effects of GM-CSF, IL-2, IFN-gamma, TNF-alpha and IL-6 on the production of IL-1 (both secreted and cell associated) and TNF-alpha by peripheral blood monocytes were studied. Monocytes were cultured for 20 h in suspension and in serum-free conditions which minimized background stimulation of monokine production. GM-CSF, IL-2 and TNF-alpha directly induced the production of cell-associated IL-1 but little or no IL-1 or TNF-alpha secretion. Combination of GM-CSF with IFN-gamma, IL-2 or TNF-alpha synergistically enhanced IL-1 secretion and had an additive effect on cell-associated IL-1 production. Combination of IL-2 with IFN-gamma or TNF-alpha also synergistically enhanced IL-1 secretion but the effect on cell-associated IL-1 production was less than additive. GM-CSF synergistically enhanced TNF-alpha secretion induced by IFN-gamma but not by lipopolysaccharide. GM-CSF did not enhance TNF-alpha secretion induced by IL-2 or TNF-alpha. In contrast, IL-2 synergistically enhanced TNF-alpha secretion induced by IFN-gamma. These results are discussed in relation to cytokine involvement in rheumatoid arthritis.
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PMID:Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-6 on the production of immunoreactive IL-1 and TNF-alpha by human monocytes. 190 83

A 53-year male patient, treated for rheumatoid arthritis with sulphasalazine, developed a total agranulocytosis. When this state had prevailed for at least 10 d no bone marrow granulocyte progenitor cells were detectable. Intravenous GM-CSF treatment was initiated 5 d later, and the patient recovered within the next 6 d. GM-CSF treatment for severe agranulocytosis deserves further investigation.
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PMID:Treatment of drug-induced agranulocytosis with recombinant GM-CSF. 206 17

A liquid culture technique was used to study 23 synovial fluids (SF) (21 from inflammatory joint diseases and 2 noninflammatory SF) and supernatants of two cultured rheumatoid arthritis (RA) synovial tissues for colony-stimulating factor (CSF). The proliferative responses of human peripheral blood macrophage-depleted non-T cells treated with synovial fluids, supernatants of synovial tissue explants, and recombinant granulocyte-macrophage (rGM)-CSF were compared. Aggregates of cells that formed in long-term cultures (15 d) were similar for each applied agent and consisted of macrophages, eosinophils, and large blasts. Tritiated thymidine incorporation was proportional to the concentration of rGM-CSF and was accompanied by an increase in number and size of cellular aggregates formed in the cultures. CSF activity was observed in inflammatory SF, with tritiated thymidine uptake of 3,501 +/- 1,140 cpm in the presence of RA samples (n = 15) compared to 1,985 +/- 628 for non-RA inflammatory SF (n = 7) (P less than 0.05) and 583 +/- 525 for medium (n = 6) (P less than 0.01). The proliferative response to RA SF was often more apparent when the samples were diluted, because at higher concentrations the RA SF was inhibitory. Two RA SF were fractionated by Sephadex G100 column chromatography; low levels of CSF activity were detected in fractions corresponding to Mr of 70-100 kD, but the major CSF activity was found in the 20-24-kD fractions. A polyclonal rabbit anti-GM-CSF antibody eliminated the stimulating activity from both rGM-CSF and RA SF. Finally, a specific RIA identified significant levels of GM-CSF (40-140 U/ml) in the culture supernatants of 3 additional RA synovial tissues. These data document the local production of GM-CSF in rheumatoid synovitis and are the first description of this cytokine at a site of disease activity.
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PMID:Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions. 264 20

After 21-48 h in culture, 2-8% of human peripheral blood monocytes strongly express terminal N-acetylglucosamine (GlcNAc) on their membranes. This can be detected with a monoclonal antibody selected for binding to asialo-agalacto-fetuin, and is eliminated by incubating the cells in pure N-acetylglucosaminidase. Expression of GlcNAc is transient, and can no longer be detected by day 4. These cells are a subset of macrophages since they are positive for non-specific esterase and stained by the monoclonal antibody EBM 11. GlcNAc-positive cells showing double staining with monoclonal antibodies UCHM1 and RFD7 were detected. Their numbers were not influenced by the addition of GM-CSF, IFN-gamma, 1,25-(OH)2 cholecalciferol or indomethacin. Macrophages which give membrane staining for terminal GlcNAc were also found in rheumatoid synovial fluid, and in synovial tissue, though in the peripheral blood their frequency was the same in samples from normal donors and from patients with rheumatoid arthritis. Immunoblots of 24-48-h monocyte cultures or of fresh synovial fluid cells using the anti-GlcNAc monoclonal, show the anticipated agalactosyl IgG heavy chains, and an additional band of 70-80kDa.
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PMID:Membrane N-acetylglucosamine: expression by cells in rheumatoid synovial fluid, and by pre-cultured monocytes. 268 54

Cytokines likely play a role in the pathogenesis of rheumatoid arthritis and other chronic inflammatory arthritidies. Recent studies on the cytokine profile of inflammatory synovitis have provided insight into the mechanisms of cellular activation in the inflamed joint. Although gamma interferon has been proposed as a major macrophage activating factor and inducer of class II major histocompatibility antigens in the joint, studies using sensitive and specific immunoassays have shown that the concentration of this lymphokine in synovial fluid is probably not sufficient to account for the high level of HLA-DR expression on Type A synoviocytes and macrophages in the joint. In contrast, GM-CSF has recently been identified in synovial effusions of patients with rheumatoid arthritis and is produced by synovial tissue cells in vitro. Like gamma interferon, GM-CSF is a known macrophage activating factor and induces HLA-DR on cells of macrophage lineage. Furthermore, supernatants of cultured synovial tissue cells contain an HLA-DR inducing factor that is neutralized by specific antibodies to GM-CSF but not by antibodies to gamma interferon. These data suggest that GM-CSF plays a significant role in macrophage activation in the synovium.
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PMID:Cytokines in chronic inflammatory synovitis. 315 Jul 93

Endothelial cells express adhesion molecules and release free forms (e.g., sELAM-1, sGMP-140, sICAM-1 and sVCAM-1). Compared with controls, the serum levels of these soluble adhesion molecules (SAM) were significantly increased in patients with rheumatoid arthritis. We investigated whether this was associated with the circulating cytokines and changes in peripheral blood T-lymphocyte (T-PBL) subsets. In healthy subjects, sELAM-1 correlated with the serum levels of Il-1 beta, Il-1 receptor antagonist (Il-1RA) and Il-6, while sGMP-140 was associated with Il-8, and sVCAM-1 was related to Il-7 and Il-8. Thus, already in controls, relations exist between the levels of SAM and circulating cytokines. The rheumatoid arthritis patients with low and high serum levels of IgA- and/or IgM-rheumatoid factors (RF) were separately analyzed. They have different cytokine profiles and showed distinct correlations. In patients with low RF, sGMP-140 and sVCAM-1 correlated with Il-1 beta, while sICAM-1 was associated with Il-7 and TNF-alpha. In patients with high RF, sELAM-1 correlated with Il-1RA, and sGMP-140 was associated with many cytokines (e.g., GM-CSF, MIP-1 alpha and TNF-alpha). In addition, lymphopenia (less than 1000 lymphocytes/microliters) was shown in 30% of the patients, and 20% (mostly with low RF levels) had reduced levels of "primed" CD45RO+ cells among T-PBL. In controls, cytokines (Il-7, Il-8 and GM-CSF), but not SAM, were associated with less CD45RO+ T-PBL. In patients with low RF only, sGMP-140 and sELAM-1 correlated with the depletion of "primed" CD4+ and CD8+ T-PBL respectively. In such patients, Il-1 beta and GM-CSF also correlated with less CD8+, CD45RO+ T-PBL. Thus, particularly in patients with low RF, increased SAM, possibly released by the endothelial cells, might reflect the cytokine-induced activation of the vascular endothelium and the extravasation of some CD45RO+ T-PBL.
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PMID:Increased soluble endothelial adhesion molecules in rheumatoid arthritis correlate with circulating cytokines and depletion of CD45RO+ T-lymphocytes from blood stream. 753 32

In this study, 100 synovial fluid (SF) samples from patients with a variety of arthritides were assayed for levels of colony-stimulating factors (CSFs) using a human bone-marrow bioassay and enzyme immunoassays for granulocyte (G-) and granulocyte-macrophage (GM-) CSFs. GM-CSF was found more frequently in samples from rheumatoid arthritis (RA) subjects (49%) than in non-RA samples (29%). Absence of GM- but not G- or bioassay CSFs characterised samples from subjects with psoriatic arthritis and ankylosing spondylitis (n = 14). There was strong evidence of an antagonistic relationship between levels of G- and GM-CSFs in samples from RA patients, an effect independent of drug treatment. However, treatment with non-steroidal anti-inflammatory agents (NSAIDs) may affect reported CSF concentrations: G-CSF levels were significantly lower in samples from subjects not taking NSAIDs. These results suggest that SF-CSF estimations using commercially available assays could provide useful diagnostic clues for clinicians, but careful interpretation is warranted particularly in patients on long-term NSAID treatment.
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PMID:Measurement of colony-stimulating factors in synovial fluid: potential clinical value. 753 53


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