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)

The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.
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PMID:Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis. 876 7

As in previous years, throughout 1995 biologic agents have been explored and tested in open and controlled clinical trials with regard to their efficacy in treating autoimmune rheumatic diseases, especially rheumatoid arthritis. Promising data have been collected from a placebo-controlled double-blind four-center study of a monoclonal anti-tumor necrosis factor-alpha antibody in rheumatoid arthritis patients. This type of treatment was demonstrated for the first time to effectively interfere with ongoing inflammatory processes in this disease entity. That anti-tumor necrosis factor-alpha treatment principles are of clinical value has also been shown in open trials applying tumor necrosis factor receptor constructs. Although undoubtedly the progress in the development of biologic agents for the treatment of inflammatory rheumatic diseases is steadily improving, new and unexpected side effects must be carefully controlled.
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PMID:Biologic agents in the treatment of inflammatory rheumatic diseases. 879 78

A review of the literature concerning the effects of traditional antirheumatic drugs on cytokines and the cytokine and anticytokine approaches already used in the therapy of rheumatoid arthritis (RA) is presented. Many antirheumatic drugs are capable of cytokine modulation in vitro. Corticosteroids inhibit the transcription of a broad spectrum of genes including those encoding monocyte, T cell-derived cytokines and several hemopoietic growth factors, whereas drugs such as cyclosporin A and D-penicillamine interfere with T cell activation more specifically by suppressing interleukin 2 (IL-2) production. The in vivo effects of drug therapy on cytokines in RA patients are less well established. Gold compounds reduce circulating IL-6 levels and the expression of monocyte-derived cytokines, such as IL-1, tumor necrosis factor (TNF), and IL-6, in the rheumatoid synovium. Decreases in circulating IL-6, soluble IL-2 (sIL-2R), and TNF receptors and in synovial fluid IL-1 levels have been reported with methotrexate. Reductions in circulating IL-6 and sIL-2R concentrations have also been observed with cyclosporin and corticosteroids, whereas azathioprine reduces IL-6 but not sIL-2R. Studies on sulfasalazine are conflicting and the in vivo effects of D-penicillamine and antimalarials have not been studied yet. Interferon gamma therapy is not effective in RA but may prove a useful antifibrotic for systemic sclerosis. Colony stimulating factors improve the granulocytopenia associated with Felty's syndrome or drug toxicities but can induce arthritis flares and should be reserved to treat infectious complications. Promising results are being obtained with selective antagonism of TNF and IL-1 in RA, and combinations of anticytokine strategies with traditional antirheumatic drugs have been already envisaged. These should preferably be based in a broader knowledge of the effects of antirheumatic agents on the cytokine network.
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PMID:Effects of antirheumatic agents on cytokines. 883 13

Rheumatoid arthritis is a T cell-mediated autoimmune disease. The lack of knowledge of the involved target antigens severely hampers research on relevant T cells in patients. Here we describe the functional analysis of freshly isolated T cells from the peripheral blood and the site of the lesion (synovial fluid or synovial membrane) of patients with rheumatoid arthritis. Healthy donors and osteoarthritis patients served as controls. Using various polyclonal stimuli, we analyzed CD4+ T cells with respect to proliferation and their ability to produce lymphokines. Our data show that lesion-derived CD4+ T cells of patients with rheumatoid arthritis are severely defective in proliferation and lymphokine (interleukin-2, interleukin-4, tumor necrosis factor-alpha, interferon-gamma) production. This activation defect was most pronounced at lower cell densities and was present in both synovial fluid derived and synovial membrane derived CD4+ T cells of all patients tested. No difference was found between responses of synovial fluid derived CD4+ T cells from osteoarthritis patients and those observed with peripheral blood derived T cells from all groups. The observed defect in lesion-derived CD4+ T cells from rheumatoid arthritis patients was not due to the effect of inflammatory factors in the synovial fluid because preincubation with synovial fluid could not induce a similar defect in control T cells. Together, our data show a rheumatoid arthritis specific, general defect in the activation of lesion-derived CD4+ T cells.
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PMID:Functional analysis of synovial fluid and peripheral blood T cells from patients with rheumatoid arthritis. 883 94

Recently it was shown that tumor necrosis factor-alpha (TNF) receptors on neutrophils may be down-regulated after stimulation with proinflammatory mediators. Since in rheumatoid arthritis neutrophils are likely to encounter these mediators in the circulation, we tested the hypothesis that rheumatoid arthritis neutrophil TNF receptors are down-regulated. Peripheral blood neutrophils from patients with rheumatoid arthritis and healthy subjects were compared with respect to their TNF binding activity and ability to be primed by TNF. There were no differences between rheumatoid arthritis and control neutrophils in receptor-mediated TNF binding, superoxide release in response to agonist, and TNF priming of this respiratory burst or in the ability to degrade cartilage in vitro and TNF priming for increased cartilage damage. It is evident that rheumatoid arthritis blood neutrophils retain the ability to bind TNF and can be primed by TNF for increased oxygen radical production and augmented cartilage damage. These findings further implicate the role of neutrophils in the pathogenesis of arthritis.
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PMID:Tumor necrosis factor priming of peripheral blood neutrophils from rheumatoid arthritis patients. 884 Feb 23

Nitric oxide (NO), a mediator of cardiovascular homeostasis, neurotransmission, and immune function, has recently been found to have important effects in bone. Both constitutive and inducible forms of NO synthase are expressed by bone-derived cells, and cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF), and interferon gamma (IFN-gamma), are potent stimulators of NO production. When combined with other cytokines, IFN-gamma markedly induces NO production, which suppresses osteoclast formation and activity of mature osteoclasts. This "superinduction" of NO is largely responsible for the selective inhibitory effect of IFN-gamma on cytokine-induced bone resorption. High concentrations of NO are also inhibitory for cells of the osteoblast lineage, and NO production appears to be partly responsible for the inhibitory effects of cytokines on osteoblast proliferation. At lower concentrations, however, NO has different effects. Moderate induction of NO potentiates bone resorption, and the constitutive production of NO at low concentrations promotes the proliferation of osteoblast-like cells and modulates osteoblast function. NO therefore appears to be an important regulatory molecule in bone with effects on cells of the osteoblast and osteoclast lineage and represents one of the molecules produced by osteoblasts which directly regulate osteoclastic activity. Stimulation of NO production in bone by proinflammatory cytokines raises the possibility that NO may be involved as a mediator of bone disease in conditions associated with cytokine activation, such as rheumatoid arthritis, tumor associated osteolysis, and postmenopausal osteoporosis.
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PMID:Nitric oxide and bone. 885 40

Patients on chronic dialysis treatment often have reduced lean body mass. Certain aspects of bio-incompatibility in dialysis can be viewed as leading to a chronic inflammatory state. In most chronic inflammatory diseases, loss of mean body mass is independent of reduced caloric intake. However, reduced caloric intake accounts for most of the weight loss in these patients and also dialysis patients. Refeeding is associated with increased fat deposition more than restoration of muscle mass. In addition to reduced caloric intake, patients with rheumatoid arthritis, a classic example of a chronic inflammatory disease, have an elevated resting energy expenditure associated with decreased lean body mass. Elevated cellular tumor necrosis factor (TNF) and IL-1 beta production can be demonstrated in these patients. However, in many dialysis patients, increased cytokine production can be 'normal' or reduced. This takes place as the level of malnutrition increases. Thus, cytokines such as IL-1 and TNF play a decreasing role in the pathogenesis of loss of body mass as malnutrition increases and curtails the synthesis of cytokines. Similar to patients with AIDS, progressive disease in patients on chronic dialysis may exhibit subclinical malnutrition which leads to decreased cytokine production. Reduction in cytokine production can be viewed as a protective mechanism.
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PMID:Mechanisms of loss of lean body mass in patients on chronic dialysis. 889 34

The role of transcription factor NF-kappa B in the induction of cytokines and ICAM-1 upon stimulation with proinflammatory cytokines, IL-1 and tumor necrosis factor (TNF)-alpha was investigated in primary synovial fibroblasts obtained from patients with rheumatoid arthritis (RA). Nuclear translocation of NF-kappa B was demonstrated after 30 min of treatment with IL-1 or TNF-alpha. Thereafter, the production of several cytokines including granulocyte macrophage colony stimulating factor, IL-6 and IL-8, that are known to be abundantly produced in the synovial cavity of RA patients, was greatly augmented. Similarly, cell surface expression of ICAM-1 was induced by the IL-1 or TNF-alpha treatment. Since expression of these genes is induced in rheumatoid synovial tissue, this experimental system is considered to represent the in vivo situation of RA pathophysiology. Using this cell culture system we attempted to modulate the intracellular signaling cascade for NF-kappa B activation and examined the effects of N-acetyl-L-cysteine (NAC) and acetylsalicylic acid (aspirin), which were previously reported to inhibit NF-kappa B activation. Pretreatment of the primary synovial fibroblasts with NAC inhibited nuclear translocation of NF-kappa B. Subsequently, the induction of these cytokines and ICAM-1 was considerably suppressed. On the other hand, pretreatment with aspirin blocked these phenomena only partially. These observations indicate the pivotal role of NF-kappa B in RA pathogenesis thus highlighting the possibility of a novel therapeutic strategy.
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PMID:Induction of cytokines and ICAM-1 by proinflammatory cytokines in primary rheumatoid synovial fibroblasts and inhibition by N-acetyl-L-cysteine and aspirin. 892 27

The cytokines interleukin-1 and tumor necrosis factor contribute to the pathogenesis of inflammatory diseases and, potentially, to atherogenesis. The synthesis of these cytokines in humans can be suppressed by oral intake of n-3 polyunsaturated fatty acids. This mechanism may contribute to the beneficial effect of long-term n-3 fatty acid supplementation in inflammatory diseases such as renal transplant rejection, immunoglobulin A nephropathy and rheumatoid arthritis.
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PMID:n-3 polyunsaturated fatty acids and human cytokine synthesis. 892 90

The effects of 12 wk of progressive resistance strength training on in vivo and in vitro immune parameters were evaluated in a controlled study of eight subjects with rheumatoid arthritis (RA), eight healthy young (22-30 yr), and eight healthy elderly (65-80 yr) individuals. Six healthy elderly (65-80 yr) nontraining control subjects were also evaluated to account for seasonal and psychosocial effects. Training subjects exercised at 80% of their one-repetition maximum and performed eight repetitions per set, three sets per session on a twice weekly basis. Peripheral blood mononuclear cell (PBMC) subpopulations, cytokine and prostaglandin (PG) E2 production, proliferative response, and delayed type hypersensitivity (DTH) skin response were measured before and after 12 wk of training. Training did not induce changes in PBMC subsets, interleukin (IL)-1 beta, tumor necrosis factor-alpha (TNF), IL-6, IL-2, or PGE2 production, lymphocyte proliferation, or DTH response in any of the training groups, compared with control subjects. These data suggest that 12 wk of high-intensity progressive resistance strength training does not affect immune function in young or elderly healthy individuals or subjects with RA.
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PMID:Effects of progressive resistance training on immune response in aging and chronic inflammation. 893 85


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