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)

Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis. The possibility was tested that interleukin-8 (IL-8), which is a cytokine that is chemotactic for lymphocytes and neutrophils, is also angiogenic. Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells. Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha. An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity. These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis, tumor growth, and wound repair.
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PMID:Interleukin-8 as a macrophage-derived mediator of angiogenesis. 771 53

Two types of tumor necrosis factor receptors have been characterized, both capable of transmitting the signal and exerting the biological functions of TNF and lymphotoxin. We measured the plasma concentrations of two types of TNF binding proteins (sTNFR-A and sTNFR-B) in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA) using an enzyme-linked binding assay. In normal controls (n = 43), mean plasma concentrations were 1030 +/- 55 and 1461 +/- 59 pg/ml for sTNFR types A and B, respectively. In 67 patients with moderate RA, mean levels were 1422 +/- 82 pg/ml (type A) and 2088 +/- 109 pg/ml (type B); in 34 patients with severe RA, 2588 +/- 279 pg/ml and 4494 +/- 550 pg/ml, respectively, were measured (P less than 0.0001 compared to normal controls). Concentrations of both type A and type B sTNFR were highly correlated in severe RA (R2 = 0.7) but not in SpA or normal controls. T lymphocytes in synovial fluid of patients with RA expressed predominantly type A TNF receptors on their surface; in some patients a weaker expression of type B receptors was also detectable. Soluble TNF binding proteins in patients with RA were able to neutralize TNF in a cytotoxicity assay, demonstrating their ability to act as "TNF-inhibiting factors". We conclude that both types of TNF receptors are parameters of disease activity in RA and may also act as TNF antagonists.
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PMID:Elevated TNF receptor plasma concentrations in patients with rheumatoid arthritis. 131 22

We previously proposed the hypothesis that the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) based on our observations that it is the dominant inducer of interleukin-1 (IL-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) production in RA synovial joint mononuclear (MNC) cells in culture. Since TNF-alpha acts via two membrane receptors, we have extended those studies to investigate the distribution of the p55 and p75 TNF receptors (TNF-R) in RA tissue. Surface receptor expression was quantitated by flow cytometry using monoclonal antibodies specific to the p55 (HTR-9) and the p75 (UTR-1) TNF-R. Both receptors were significantly increased on MNC isolated from the synovial membrane of RA patients compared to normal or RA peripheral blood MNC. Interestingly, the p75 TNF-R was increased both on large monocytic/macrophage-type cells and CD3+ lymphocytes. Furthermore, there was a significant increase in the proportion of CD3+ cells in RA synovial fluid expressing the p75 TNF-R, compared to matched peripheral blood MNC. In contrast to RA synovial MNC, p75 or p55 TNF-R expression was not significantly increased in osteoarthritis synovial MNC. In addition, Northern blot analysis indicated abundant expression of both p55 and p75 mRNA in RA synovial joint MNC. This was in contrast to normal peripheral blood MNC cells which contained little or no constitutive TNF-R mRNA; following stimulation with phytohemagglutinin and IL-2, a rapid and transient expression of both receptor mRNA was induced. These results, therefore, indicate that in RA synovial joint tissue there is up-regulation of both p55 and p75 TNF-R mRNA and surface protein expression, and with the presence of TNF-alpha in RA tissues, these results provide support to our hypothesis that TNF-alpha is of critical importance in the pathogenesis of RA.
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PMID:Enhanced expression of tumor necrosis factor receptor mRNA and protein in mononuclear cells isolated from rheumatoid arthritis synovial joints. 132 May 71

Rapid expression of mRNA encoding vascular cell adhesion molecule-1 (VCAM-1) was induced by tumor necrosis factor (TNF) in fibroblast-like cells obtained from synovial tissue. Both alternatively spliced forms of VCAM-1 mRNA were detected by polymerase chain reaction in TNF-stimulated fibroblast-like synoviocytes. Western blotting analysis showed that two distinct proteins, reactive with an anti-VCAM-1 anti-sera, were expressed by 2 hours of TNF stimulation in both synoviocytes and human umbilical cord vein endothelial cells (HUVEC). The majority of HUVEC and synoviocytes displayed VCAM-1 surface expression after several hours of TNF stimulation. In contrast, dermal fibroblasts upregulated intercellular adhesion molecule-1 (ICAM-1) but not VCAM-1 expression in response to TNF. These results indicate that VCAM-1 and ICAM-1 expression can be differentially regulated and suggest tissue specific regulation of VCAM-1 expression. Furthermore, these findings may provide an explanation for the chronic retention and activation of long-lived lymphocytes and monocytes, which express VLA-4 (the receptor for VCAM-1), in the synovium in rheumatoid arthritis.
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PMID:Expression of vascular cell adhesion molecule-1 in fibroblastlike synoviocytes after stimulation with tumor necrosis factor. 137 88

Rheumatoid arthritis is a complex inflammatory disease of unknown cause. Although various laboratory and clinical measurements are useful in managing these patients, there is a need for better tests to quantitatively assess disease activity. The purpose of this study was to investigate the association of certain immune and inflammation (I-I) parameters with four traditional disease severity measures and a functional measure in rheumatoid arthritis patients. A single set of patient blood samples was analyzed, and four traditional disease severity measures and patient functional statuses were determined from 64 consecutive outpatients with rheumatoid arthritis. Plasma tumor necrosis factor-alpha (TNF), soluble interleukin-2 receptor (sIL-2R), sCD4 and sCD8 (and the sCD4/sCD8 ratio), neopterin, and fibrin D-dimer were analyzed in relationship to Westergren erythrocyte sedimentation rate (ESR), physician assessment of disease activity, joint pain count, grip strength, and Arthritis Impact Measurement Scale (AIMS) scores. Rheumatoid arthritis patients had higher mean levels of all I-I measures (except sCD4) compared to healthy subjects. Initial significant correlations between TNF, sIL-2R, and D-dimer and several disease severity and functional measures were detected. When we controlled for the covariates age, gender, race, and medications, regression analyses indicated that, as a group, the I-I measures were significantly related to grip strength, physician disease severity rating, ESR, and total joint pain. When the predictive values of the I-I measures were tested controlling for the covariates and ESR, D-dimer was independently and significantly associated with variability in grip strength, physician disease severity, and AIMS physical disability, while TNF was associated with a significant amount of variability in total joint pain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disease severity in rheumatoid arthritis: relationships of plasma tumor necrosis factor-alpha, soluble interleukin 2-receptor, soluble CD4/CD8 ratio, neopterin, and fibrin D-dimer to traditional severity and functional measures. 143 Jan 6

As many as 39 patients aged 16-70 years with rheumatoid arthritis (RA) lasting 3 months to 20 years were examined. The diagnostic titers of rheumatoid factor were discovered in 23 patients. The control group was made up of 26 healthy subjects (donors). The activity of IL-1 in supernatants of peripheral blood monocytes (PBM) was measured by bioassay resting on co-stimulation of mouse thymocytes; quantitative determination of tumor necrosis factor-alpha (TNF-alpha) was made by ELISA, PGE2 was determined by RIA. As compared to the controls, the RA patients manifested an increase of the production of IL-1 beta, TNF-alpha and PGE2 of PBM, which rose with the disease activity. The RA patients demonstrated direct correlations between the level of IL-1 beta, TNF-alpha and PGE2 in supernatants of PBM, whereas the donors showed up a negative correlation between IL-1 beta activity and PGE2.
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PMID:[Changes in the production of monokines and prostaglandin E2 by the peripheral blood monocytes in patients with different clinico-immunological variants of rheumatoid arthritis]. 145 68

It is now generally accepted that many cytokines are involved in the pathogenesis of autoimmune disease, either directly by causing tissue destruction or indirectly through the activation of autoreactive and inflammatory cells. Thus, cytokines, such as tumor necrosis factor-alpha, are implicated in the pathogenesis of rheumatoid arthritis based on in vitro studies on synovial tissue from patients with rheumatoid arthritis, which suggest that the effects of tumor necrosis factor-alpha are amplified by its potential to induce other pro-inflammatory cytokines, such as interleukin-1 and granulocyte-macrophage colony-stimulating factor. Transgenic mouse technology has shown that mice expressing the human tumor necrosis factor-alpha gene develop a polyarthritis. Interleukin-2 has also been identified by transgenic technology as a cytokine involved in the pathogenesis of insulin-dependent diabetes mellitus through the activation and stimulation of growth of autoreactive T cells.
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PMID:Cytokines in autoimmunity. 146 99

The interleukin-6-(IL-6)-alpha dependent B-cell heterohybridomas were obtained by the fusion of X65.Ag8.653 cells with spleen cells from August rats immunized with lipopolysaccharide E. coli. One of these hybridomas (D6C8) was found to be most dependent on IL-6 for its surviving and growth. Human recombinant IL-1 beta and tumor necrosis factor-alpha could not induce the in vitro growth of this cell line. Presence of elevated level of IL-6 was demonstrated in the sera of patients with rheumatoid arthritis. A specific and sensitive detection of the IL-6 activity in test samples makes it possible to study the presence and role of IL-6 in various immunological disorders.
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PMID:[The production and characteristics of an interleukin-6-dependent hybridoma]. 146 86

The 1991 literature on septic arthritis included a concise review of adult septic arthritis, examples of pseudoseptic arthritis, and two interesting animal studies. One animal study examined the induction of acute synovitis by the intra-articular injection of bacterial endotoxin and the cytokines tumor necrosis factor-alpha, and interleukin-1 beta; and the other studied the effects of early and delayed synovectomy in the management of septic arthritis. The predispositions to septic arthritis can be divided into local joint abnormalities, systemic factors, or both. Examples of the local joint abnormalities include osteoarthritis of the hip and apatite-associated arthropathy. Septic arthritis in a patient with rheumatoid arthritis, in a patient with diabetes mellitus and hip arthropathy associated with hemochromatosis, or in a patient with acquired immunodeficiency syndrome and hemophilic arthropathy are examples of how systemic predisposition is coupled with local joint pathology to increase the vulnerability of the host to joint infection. Other examples of systemic disease that predispose to septic arthritis are systemic lupus erythematosus, hypogammaglobulinemia, and human immunodeficiency virus infection, as well as intravenous drug abuse. Unusual microorganisms causing septic arthritis in the adult include Achromobacter xylosoxidans, Moraxella catarrhalis, meningococci, and diphtheroids. Uncommon pathogenesis is represented by a case of intra-articular inoculation of Mycobacterium gastri into the small joint of the hand and a case of mixed bacterial infection of the hip resulting from an extension of a contiguous pelvic infection associated with trauma. Two cases of immune complex glomerulonephritis illustrate the extra-articular complications of septic arthritis: one due to group G streptococcus and the other due to pneumococcus. Finally, septic bursitis is reviewed from the community practice perspective.
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PMID:Bacterial arthritis. 150 74

This study reports on leukemia inhibitory factor (LIF) in human articular connective tissues. Biologically active LIF is present in synovial fluids from patients with osteoarthritis and at higher titers in samples from patients with rheumatoid arthritis. Cultured human synoviocytes and articular chondrocytes produced biologically active LIF and synthesized and secreted LIF proteins that migrated in SDS PAGE at approximately 43 kD. This was increased after stimulation with IL-1 beta. Chondrocytes in serum-containing cultures expressed the 4.2-kb LIF mRNA. IL-1 beta, LPS, and to a lesser extent tumor necrosis factor-alpha induced LIF gene expression. LIF autoinduced its mRNA and this provides evidence for an effect of this cytokine on function of joint tissue cells. Among a series of growth factors tested, transforming growth factor (TGF beta), including the isoforms TGF-beta1, TGF-beta 2, and TGF-beta 3, platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor induced this cytokine gene but differed with respect to the duration of their effects. Cultured synoviocytes expressed the LIF gene in response to the same set of peptide regulatory factors. Analysis of signal transduction pathways showed that PMA increased LIF mRNA, whereas calcium ionophore and cAMP had no detectable effects. Cycloheximide was a potent LIF mRNA inducer and dexamethasone inhibited LIF induced by PMA or IL-1 beta. Cartilage organ cultures and synovial tissues stimulated with IL-1 expressed high levels of LIF mRNA as demonstrated by in situ hybridization. These results identify LIF as a new cytokine that is produced by joint tissue cells and is overexpressed in arthritis. The induction of this cytokine by factors that are present during joint inflammation and the effects of LIF on connective tissue cells suggest that LIF is a mediator that can contribute to the pathogenesis of arthritis.
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PMID:Leukemia inhibitory factor is expressed in cartilage and synovium and can contribute to the pathogenesis of arthritis. 152 40


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