Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The capacity of synoviocytes to participate in inflammatory responses may be altered by the cytokine-enhanced expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). To examine this possibility, the ability of selected cytokines to enhance ICAM-1 expression was examined. The data indicated that each of these cytokines (interleukin-1 beta greater than tumor necrosis factor-alpha, interferon-gamma much greater than interleukin-6) can up-regulate synoviocyte ICAM-1 expression. This can potentially increase the ability of these cells to interact with infiltrating inflammatory cells, thereby propagating immunologically mediated inflammation such as occurs in rheumatoid synovitis.
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PMID:Regulation of the expression of adhesion molecules by human synoviocytes. 160 27

Cell-free synovial fluid (SF) obtained from patients with rheumatoid arthritis contains a helper factor(s) capable of augmenting the generation of plaque-forming cells (PFC) in pokeweed mitogen (PWM)-stimulated normal peripheral blood mononuclear cells (PBMC). This helper factor behaves like a polyclonal B-cell activator, in that it triggers the formation of IgM, IgG, and IgA PFC. However, SF has little or no effect on the proliferation of PWM-activated PBMC. Furthermore, SF was capable of replacing T cells for PWM-induced differentiation but not proliferation of enriched human blood B lymphocytes. No helper factor or T-cell-replacing activity was found in SF from patients with traumatic synovitis. Fractionation of SF containing helper activity on staphylococcal protein A column indicated that the activity is induced by biologically active molecules distinct from materials that preferentially bind to protein A such as IgG immune complexes. We conclude that the present activity has striking similarities to the recently described B-cell differentiation factor that is produced by specifically activated T-cell lines in vitro.
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PMID:Demonstration of a helper factor(s) with T-cell-replacing activity in synovial fluid. 624 Jan 13

We report a patient with polymyalgia rheumatica (PMR) accompanied by an increased Rheumatoid Arthritis Hemagglutinin Test (RAHA) titer and interleukin-6 level in the synovial fluid. A 60-year-old female was admitted because of polymyalgia, a body temperature of 39.2 degrees C, and an erythrocyte sedimentation rate increased to 94 mm/h. Since a muscle biopsy failed to show a specific finding, she was diagnosed as PMR. The titer of RAHA and the interleukin-6 level were increased only in the synovial fluid; prednisolone treatment decreased both. The present case raised the possibility that a similar mechanism in rheumatoid arthritis may involve the development of synovitis in PMR.
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PMID:Increased RAHA titer and interleukin-6 levels in the synovial fluid in a patient with polymyalgia rheumatica. 824 93

Interleukin-6 (IL-6) was detected at low levels in plasma [0.014 +/- 0.006 ng/ml (mean +/- SEM] and in high amounts in synovial fluid [SF; 2.6 +/- 2.2 ng/ml (mean +/- SEM)] of patients with rheumatoid arthritis. No correlation of IL-6 levels in plasma or SF with the ESR (n = 15) or with histological parameters of acute local synovitis (n = 10) was observed. In contrast, SF IL-6 was positively correlated with histological characteristics of chronic synovitis (n = 10; P < or = 0.01) and elevated plasma IgG concentrations (n = 15; P < or = 0.05). In vitro concentrations of IL-6 comparable to those detected in SF increased the production of both IgG and IgM by synovial membrane mononuclear cells. The present results contribute to the view that high local IL-6 concentrations in SF promote chronic synovitis in RA.
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PMID:Interleukin-6 in synovial fluid is closely associated with chronic synovitis in rheumatoid arthritis. 782 40

We have investigated the temporal relationship among proinflammatory cytokine expression, nitric oxide (NO) production and joint inflammation in the acute phase of bacterial cell wall-derived peptidoglycan polysaccharide (PG/PS)-induced arthritis. Acute joint inflammation was induced in female LEW/N rats by a single intraperitoneal injection of PG/PS. Arthritis index and paw volume were quantified and joint histopathology was evaluated during acute joint inflammation (0-10 days). Tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) were determined by bioassay whereas nitric oxide (NO) was quantified by measuring serum nitrate/nitrite levels via the Griess procedure. We found that serum levels of TNF and serum IL-1 preceded the increase in IL-6 and NO production. Furthermore, the production of these proinflammatory cytokines and NO preceded bone erosion and osteoclast activity. Erosion of subchondral bone preceded pannus formation and cellular synovitis in the acute phase of PG/PS-induced arthritis. The temporal expression of TNF, IL-1, IL-6 and NO suggest a cascade of inflammatory mediators in which monocytes and macrophages respond to PG/PS with enhanced synthesis of TNF and IL-1, which may in turn promote the synthesis of IL-6 and NO. We postulate that one or more of these inflammatory events are responsible for initiating the subchondral bone erosion observed in acute joint inflammation.
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PMID:Cytokine and nitric oxide production in the acute phase of bacterial cell wall-induced arthritis. 917 27

Fluorescein isothiocyanate (FITC) was found to stain cytoplasmic granules of avian heterophilgranulocytes. In tissue sections, the fluorescent granulocytes were predominantly distributed adjacent to trabecular bones. The fluorescein stained granulocytes were abundant in synovial fluids of chickens with synovitis. A significant correlation was observed in the percent of fluorescein labeled granulocytes in blood smears and the percent of heterophils determined using an automated counting method, in unstained blood from normal and Escherichia coli-infected turkeys. The fluorescein-binding heterophils purified from chickens showed a time dependent increases in the oxidation of 2',7'-dichlorofluorescin diacetate (DCF-DA) and the reduction of nitroblue tetrazolium (NBT) which were indicative of changes in oxidative burst in response to phorbol 12-myristate 13-acetate (PMA), Salmonella typhimurium lipopolysaccharide (LPS), and zymosan A (ZA). These heterophil-activating agents, also, caused significant degranulation at 16 h post-treatment, as indicated by the loss fluorescence. There were microscopically visible alterations in the cell shapes and a decrease in the density of granules due to treatment with LPS, PMA or ZA. In addition, these cells also showed phagocytic response which was evident at 30 min of incubation with fluorescent latex particles. Both chicken and turkey heterophils produced interleukin-6 in vitro at 24 h in response to LPS but not to PMA, FMLP or ZA. The chicken heterophils showed spontaneous production of matrix metalloproteinases (MMP) which was significantly enhanced by treatment with LPS, PMA, and ZA; however, LPS appeared to be most effective in inducing MMP production. These results demonstrate that the functions of heterophils can be differentially regulated by different activating agents and the fluorescein binding property of these cells may be useful for their histochemical identification.
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PMID:Fluorescein isothiocyanate staining and characterization of avian heterophils. 965 33

Interleukin-6 (IL-6) is highly produced during arthritis but its exact function is still unknown. In this study we examined if IL-6, apart from its role in immunity, was involved in the local inflammatory response in experimental arthritis. IL-6 deficient (IL-6(-/-)) and wild-type mice were first compared in the antigen-induced arthritis model. IL-6 deficiency resulted in a mild, transient inflammation whereas wild-type mice developed a chronic, destructive synovitis. Wild-type mice immunized with one-tenth of the normal antigen dose still developed chronic arthritis despite low antibody levels, excluding reduced humoral immunity in IL-6(-/-) mice as a crucial phenomenon. In addition, passive immune-complex-induced arthritis did not differ between wild-type and IL-6(-/-) mice. Another option is reduced levels of Th1 cells in IL-6(-/-) mice. However, transfer of antigen-specific wild-type lymph node cells to IL-6(-/-) mice enhanced acute joint inflammation and increased cartilage damage but still could not sustain chronic inflammation, suggesting involvement of nonimmune elements of IL-6 activity in chronicity. In line with this, nonimmunologically mediated zymosan-induced arthritis developed similarly in the first week, but only wild-type mice developed chronic synovitis. These results indicate an important role for IL-6 in propagation of joint inflammation, potentially independent of its role in immunity.
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PMID:Involvement of IL-6, apart from its role in immunity, in mediating a chronic response during experimental arthritis. 1110 80

Severe combined immunodeficiency (SCID) mice were engrafted with rheumatoid arthritis (RA) synovium and evaluated to determine whether RA synovial morphology and function were maintained in the RA-SCID grafts. The four major components of RA synovitis, inflammation, immune reactivity, angiogenesis, and synovial hyperplasia persisted in RA-SCID grafts for 12 weeks. Retention of chronic inflammatory infiltrates was demonstrated by histological evaluation and by immunohistology for CD3, CD20, and CD68. Staining for CD68 also revealed that the grafts had undergone reorganization of the tissue, possibly as a result of fibroblast hyperplasia. Immune and inflammatory components were confirmed by the detection of human immunoglobulins and human interleukin-6 in serum samples obtained from grafted animals. Human blood vessels were detected by dense expression of CD31. Small vessels persistently expressed the vitronectin receptor, alpha v beta 3, a marker of angiogenesis. All vessels expressed VAP-1, a marker of activated endothelial cells. Finally, the grafts retained the ability to support immigration by human leukocytes, as demonstrated by the functional capacity to recruit adoptively transferred 5- (and -6)-carboxyfluorescein diacetate succinimidyl ester-labeled T cells. T cells entering the RA-SCID grafts became activated and produced interferon-gamma, as detected by reverse transcriptase-polymerase chain reaction analysis. These studies demonstrate that the RA-SCID model maintains many of the phenotypic and functional features of the inflamed RA synovium.
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PMID:Inflammation, immune reactivity, and angiogenesis in a severe combined immunodeficiency model of rheumatoid arthritis. 1178 29

Rheumatoid arthritis (RA) is a systemic disease that is associated with increased mortality and morbidity. Prognosis depends on disease severity and response to treatment. Those patients whose diseases are refractory to treatment with disease-modifying antirheumatic drugs (DMARDs) and have persistent inflammation have reduced survival similar to patients with triple-vessel coronary artery disease and Hodgkin's lymphoma. Although DMARDs reduce inflammation and improve symptoms, they do not improve long-term prognosis. Chronic synovial inflammation results in damage to the articular cartilage and adjacent bone. Consequently,after 10 years of disease most patients develop significant disability due to joint damage. Interleukin-6 (IL-6) is a key mediator of inflammation in RA. Inhibition of IL-6 reduces synovitis and improves symptoms. Therapies targeting IL-6 are promising new treatments for RA.
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PMID:Clinical experience with inhibition of interleukin-6. 1517 49

Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by aching and stiffness in the shoulder and in the pelvic girdles and neck. In the past, PMR was considered a manifestation of giant cell arteritis (GCA) or a variant of elderly-onset rheumatoid arthritis (EORA). The current diagnostic criteria for PMR were empirically formulated by clinical experts who had studied the disease extensively. Arthroscopic, radioisotopic and magnetic resonance imaging studies all have indicated the presence of a synovitis in proximal joints and periarticular structures. The synovitis is probably responsible for the musculoskeletal symptoms in PMR. The prominence assigned to the proximal symptoms has probably overshadowed the less well recognized and more variable distal musculoskeletal manifestations which are present in about half of the cases. A normal erythrocyte sedimentation rate does not exclude a diagnosis of PMR. C-reactive protein and interleukin-6 seem to be more sensitive indicators of disease activity both at diagnosis and during relapse/recurrence. Corticosteroids are the drugs of choice for treating PMR. A course of treatment of 1-2 years is often required. However, some patients have a chronic, relapsing course and require low doses of corticosteroids for several years. Large, multicenter, double-blind, placebo-controlled studies are required to define the role of methotrexate and anti-TNF-alpha agents as corticosteroid-sparing drugs in PMR.
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PMID:Polymyalgia rheumatica. 1545 28


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