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Interleukin-1beta in plasma and synovial fluid in relation to radiographic changes in arthritic temporomandibular joints.

The aim of this study was to investigate the level of the cytokine IL-1beta in plasma and temporomandibular joint (TMJ) synovial fluid of patients with arthropathies, and to study the relation between IL-1beta levels of synovial fluid and plasma as well as radiographic changes of the TMJ. 31 patients with general disease, 14 with rheumatoid arthritis (RA) and 17 with various arthritides were included in the study. Synovial fluid and blood samples were collected, and an individualized tomography of the TMJ was performed. Detectable levels of IL-1beta were found in 5 out of 39 synovial fluids and in 10 out of 27 plasma samples. The presence of IL-1beta in both plasma and synovial fluid was more frequent in RA patients than in the non-RA group. The extension of radiographic erosion was significantly greater in joints with IL-1beta than in those without. Both the extension of erosion and grade of radiographic changes of the TMJ were greater in patients with detectable IL-1beta level of plasma than in patients without. Our study indicates that presence of IL-1beta in plasma and synovial fluid is related to radiographic changes of the TMJ.

Adult↗

Chondronectin in human synovial fluid.

Chondronectin is a cartilage matrix protein that specifically mediates the attachment of chondrocytes to type II collagen. A monoclonal antibody to chondronectin was used in a competitive enzyme linked immunosorbent assay (ELISA) and Western blot assay to detect, measure, and characterise chondronectin in human synovial fluid. Chondronectin was detected in all 18 rheumatoid and 11 osteoarthritic synovial fluids examined. Chondronectin concentrations in synovial fluid were lower than those in plasma and correlated most strongly with concentrations of synovial fluid albumin and fibrinogen. These results suggest that synovial fluid chondronectin is in part derived from plasma. The role of chondronectin as a marker of cartilage destruction and potential mediator of pannus formation is discussed.

Albumins↗

Correlation between the appearance of gelatinases in the synovial fluid of patients with rheumatoid arthritis and polymorphonuclear elastase, stromelysin-1, and the tissue inhibitor of metalloproteinase-1.

OBJECTIVE: To clarify whether gelatinases in the synovial fluid are related to rheumatoid arthritis (RA). METHODS: Gelatinases in the synovial fluid of patients with RA were analyzed by gelatin zymography. RESULTS: We classified patients into 3 distinct groups based on the gelatinases present. Although inactive gelatinase A was found in the synovial fluid of all patients with RA, the presence of gelatinase B varied: group I contained none, group II contained inactive gelatinase B, and group III contained active gelatinase B. The presence of gelatinase B was positively correlated with the polymorphonuclear (PMN) elastase content of the synovial fluid. Furthermore, the presence of activated gelatinase B correlated well with the stromelysin-1 content. Conversely, large amounts of the tissue inhibitor of metalloproteinase-1 (TIMP-1) were found in the synovial fluid of patients in group II. CONCLUSION: The appearance and form of gelatinase B may reflect the inflammatory condition of patients with RA.

Arthritis, Rheumatoid↗

Effect of piroxicam therapy on granulocyte function and granulocyte elastase concentration in peripheral blood and synovial fluid of rheumatoid arthritis patients.

The effect of piroxicam therapy (20 mg/day for 15 days) on various polymorphonuclear granulocyte (PMN) responses and on PMN elastase concentration was investigated in nine patients with active rheumatoid arthritis. Peripheral blood and synovial fluid samples were collected before starting therapy and 12 h after the last dose of the drug. All patients were evaluable for peripheral blood analysis and six for synovial fluid analysis. Piroxicam therapy had no effect on PMN random migration and phagocytosis, while it significantly reduced both FMLP-induced aggregation and FMLP-induced chemotaxis. This seems mainly due to an effect on FMLP binding, as no differences were observed after therapy in PMA- and PHA-induced aggregation as well as in serum-induced chemotaxis. In contrast, a marked impairment of NBT test and PMA- and FMLP-induced superoxide anion (O2-) production was found after piroxicam therapy. This effect was as evident in peripheral blood as in synovial fluid PMN. Also, a significant reduction in synovial fluid PMN number and synovial fluid PMN elastase concentration (elastase-alpha 1-proteinase complex) was found after treatment. It is concluded that piroxicam may act at different sites on various PMN responses. Its effect on O2- generation and PMN elastase concentration in synovial fluid may have an important role in reducing destruction of arthritic joint tissue.

Adult↗

Glycosaminoglycan components in temporomandibular joint synovial fluid as markers of joint pathology.

PURPOSE: This study investigated the correlation between temporomandibular joint (TMJ) disease and the composition of glycosaminoglycans (GAGs) components in the synovial fluid (SF). MATERIALS AND METHODS: Synovial fluid (SF) was obtained from 30 TMJs of 28 female patients diagnosed as having a displaced disc with reduction (WR) (seven joints), a displaced disc without reduction (WOR) (13 joints), osteoarthritis (OA) (five joints), or rheumatoid arthritis (RA) (five joints) by MR imaging and clinical examination. After the SF was directly aspirated, It was digested with chondroitinase ABC and hyaluronidase, and the concentration of unsaturated disaccharide isomers of chondroitin 6-sulfate (delta di-6S), chondroitin 4-sulfate (delta di-4S) and hyaluronic acid (delta di-HA) were measured by high-performance liquid chromatography (HPLC) combined with fluorometry. The ratio of delta di-6S or delta di-4S to delta di-HA, and delta di-6S to delta di-4S, were calculated. RESULTS: There were no significant differences in concentrations of delta di-6S, delta di-4S, or delta di-HA among the groups. The ratio of delta di-6S to delta di-4S was 2.7 +/- 1.4 in OA, 2.6 +/- 0.9 in joints with WOR, 2.9 +/- 1.2 in joints with WR, and 1.3 +/- 0.4 in RA synovial fluid. Differences in the delta di-6S: delta di-4S ratio between RA and the other conditions were statistically significant (P < .05). CONCLUSION: These results suggest that the delta di-6S:delta di-4S ratio in the synovial fluid of the TMJ reflects the proteoglycan metabolism of the joint tissues, particularly of the articular cartilage and synovial tissue. This ratio could be used to diagnose joint diseases and to predict articular cartilage destruction or synovial proliferation caused by these diseases.

Adult↗

Fibronectin and lymphocytes in inflammatory tissue. Studies of blood and synovial fluid lymphocytes from patients with rheumatoid arthritis and other inflammatory arthritides.

Lymphocytes infiltrating tissues under chronic inflammatory conditions are often surrounded by deposits of fibronectin. We have studied the possibility that this reflects capacity of lymphocytes to synthesize fibronectin and compared lymphocytes from blood and synovial fluid with respect to fibronectin interactions. In vitro activated blood lymphocytes exhibited synthesis of a fibronectin-like molecule. Synovial fluid cells appeared to synthesize the same high molecular weight component spontaneously. Activated blood lymphocytes have cell surface fibronectin and surface components of lower molecular weight which could be immunoprecipitated with anti-fibronectin antibodies as well as by insolubilized collagen. Synovial fluid cells showed cell surface fibronectin as revealed by immunocytochemical detection but seemed to lack or have relatively small amounts of the low-molecular weight fibronectin-like surface components. Synovial fluid T cells from arthritis patients showed adhesion to fibronectin. Immunocytochemistry demonstrated presence of alpha 4 and alpha 5 beta 1 integrins at the surface of the synovial fluid T cells and RGD and LDV peptides inhibited adhesion of the cells to fibronectin. Noteworthy, a portion of synovial fluid cells with lymphocyte markers also bound to plastic. Blood lymphocytes from the same arthritis patients displayed relatively poor or negligible adhesion to fibronectin unless activated to blast transformation and did not attach to plastic. Taken together these results suggest that activated lymphocytes from blood and synovial fluid may use fibronectin of exogenous or endogenous origin when interacting with tissues during inflammatory processes. Furthermore, the presence at the lymphocyte surface of components of different molecular weight precipitated by anti-fibronectin antibodies suggests that fibronectin or its fragments can bind to the lymphocyte surface.

Arthritis↗

Yersinia specific immune complexes in the synovial fluid of patients with yersinia triggered reactive arthritis.

Yersinia specific immune complexes were demonstrated in the synovial fluid of three patients out of 12 with yersinia triggered reactive arthritis. They were not detectable in the synovial fluid of any of the 16 control patients, including nine with reactive arthritis triggered by factors other than yersiniae. Platelet reactive IgG was detectable in the synovial fluid of eight out of the 12 patients with yersinia triggered reactive arthritis and in three of the 16 control patients, all three having rheumatoid arthritis. An enzyme linked immunosorbent assay and a platelet 125I labelled staphylococcal protein A test were used to measure yersinia specific immune complexes and platelet reactive IgG respectively. The results obtained show for the first time the occurrence of bacterial antigens, derived from the causative strain, in the synovial fluid in yersinia triggered reactive arthritis.

Adolescent↗

Blood versus synovial fluid ethanol concentrations in humans.

Many tissues have been analyzed for their relevance in prediction of blood ethanol concentrations, with varying results. Synovial fluid is contained and protected by the bursa sac. Because of its high water content, it may be a suitable biological fluid for analysis if a linear correlation could be established between blood and synovial fluid ethanol concentrations. Blood-synovial fluid ratios of ethanol in 28 human cadavers, using an internal standard, exhibit a good distribution ratio with an average of 0.99 +/- 0.29 and a correlation coefficient of 0.89. This study shows that synovial fluid is a good alternative biological sample for prediction of blood ethanol levels within a range.

Ethanol↗

Synovial fluid gelatinase concentrations and matrix metalloproteinase and cytokine expression in naturally occurring joint disease in horses.

OBJECTIVES: To determine concentrations of matrix metalloproteinase (MMP)-2 and -9 in synovial fluid; and mRNA expression of MMP-1, -13, and -3; interleukin[IL]-1alpha and beta; and tumor necrosis factor (TNF)-alpha in synovial membrane and articular cartilage from horses with naturally occurring joint disease. SAMPLE POPULATION: Synovial fluid (n = 76), synovial membrane (59), and articular cartilage (45) from 5 clinically normal horses and 55 horses with joint disease categorized as traumatic (acute [AT] or chronic [CT]), osteochondritis dissecans (OCD), or septic (S). PROCEDURE: Synovial fluid gelatinase concentrations were analyzed, using zymography. Synovial membrane and articular cartilage mRNA expression for MMP-1, -3, and -13, IL-1alpha and beta, TNF-alpha, type-II collagen, and aggrecan were analyzed, using quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Synovial fluid pro-MMP-2 concentration was significantly higher in diseased joints than normal joints. Septic joints had significantly higher concentrations of pro and active MMP-9. Stromelysin-1 was expressed in > or = 80% of synovial membrane and articular cartilage samples and was strongly influenced by age. Collagenases were rarely expressed, with MMP-13 expressed only in diseased joints. Interleukin-1beta expression was significantly higher in all OCD samples and was influenced by age. Tumor necrosis factor-alpha expression was significantly higher in cartilage from joints with AT and OCD. There was no correlation between MMP or cytokines and type-II collagen or aggrecan expression. CONCLUSIONS AND CLINICAL RELEVANCE: Matrix metalloproteinase-2 and -3 are abundant in naturally occurring joint disease and normal joints. Interleukin-1beta and TNF-alpha may be important in the pathogenesis of OCD. Age affects MMP and IL-1beta concentrations.

Animals↗

Interleukin-1beta, interleukin-1 receptor antagonist, and interleukin-1 soluble receptor II in temporomandibular joint synovial fluid from patients with chronic polyarthritides.

PURPOSE: The aim of this study was to investigate whether interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra), or soluble IL-1 receptor II (sIL-1RII) in synovial fluid or plasma is associated with joint pain or signs of tissue destruction in patients with temporomandibular joint (TMJ) involvement of polyarthritides. PATIENTS AND METHODS: Forty-three patients with TMJ involvement of polyarthritides were included. TMJ resting pain, tenderness to palpation, pressure pain threshold, pain on mandibular movement, and anterior open bite were assessed. TMJ synovial fluid samples and plasma were obtained for analysis of IL-1beta, IL-1ra, and sIL-1RII. RESULTS: IL-1beta was detected in 18% of the synovial fluid samples and in 44% of the plasma samples. The concentrations of IL-1ra in plasma were lower than in the synovial fluid, whereas the opposite condition was found for sIL-1-RII. IL-1ra in synovial fluid and plasma was associated with low intensity of TMJ pain. sIL-1RII in synovial fluid was associated with low degree of anterior open bite, whereas sIL-1RII in plasma was associated with widespread musculoskeletal pain, TMJ pain and tenderness, and decreased pressure pain threshold over the TMJ. CONCLUSION: IL-1ra and sIL-1RII are present in different proportions in TMJ synovial fluid and blood plasma from patients with TMJ involvement of polyarthritis. Both of these molecules seem to influence the clinical features of these forms of TMJ inflammation.

Arthralgia↗

The contribution of synovial fluid lipoproteins to the chronic synovitis of rheumatoid arthritis.

Lipids in the synovial fluid of patients with active rheumatoid arthritis are elevated compared to normal synovial fluid and that of other inflammatory arthropathies. Various assumptions about the role of these lipids have been made. This study offers evidence that these lipids may contribute to the synovitis in rheumatoid arthritis through participation in the arachidonic pathway within the joint space. Phospholipase A2 activity, phospholipids, prostaglandin E2, and leukotriene B4 have been correlated in the synovial fluid and plasma of untreated rheumatoid patients and compared with that of patients with osteoarthritis.

Arthritis, Rheumatoid↗

Inhibitory factor(s) of lymphoproliferation produced by synovial fluid mononuclear cells from rheumatoid arthritis patients: the role of monocytes in suppression.

Synovial fluid (SF) and synovial fluid mononuclear cells (SFM) were obtained from patients with rheumatoid arthritis (R.A.). The SF stimulated normal blood monocytes for nitroblue tetrazolium (NBT) reduction and inhibited normal lymphocyte response to PHA. Similar activities were found in supernatants from the cultures of SFM cells. Molecular weight of the lymphocytes inhibitory factor(s) produced by SFM was in range 50,000 to 100,000. The factor exerted its inhibitory activity via monocytes and had no direct toxic or blocking effect on lymphocytes. Monocytes played an active role in suppression presumably via production of a second-step inhibitory signal(s). It is suggested that the monocytes activated by the SFM-produced factor(s) are in turn triggered on for suppression of lymphoproliferation. These studies implicate that the state of monocyte activation is important in the regulation of lymphocyte responsiveness. This model of suppression may provide some explanation for SF lymphocyte hyporeactivity to mitogens in R.A.

Arthritis, Rheumatoid↗

Cellular activation products in osteoarthritis synovial fluid.

In order to address the issue of the role of mast cells (MC) and nitric oxide (NO) in rheumatic synovial-fluid diseases, synovial fluid (SF) collected from the knee of patients with osteoarthritis (OA), articular chondrocalcinosis (ACC) or rheumatoid arthritis (RA) was examined for the levels of mast cells (MC), histamine, tryptase, phospholipase A2 and nitrite. MC counts were found to be elevated in the SF of OA patients as compared with RA patients. Histamine content in SF parallelled the number of MC. Tryptase levels were elevated in OA in comparison to RA and ACC, but the difference was not statistically significant. Identical PLA2 levels were recorded among the 3 groups. Nitrite concentrations were also higher in SF from OA patients as compared to RA patients. These results suggest that mast cells (MC), in association with various inflammatory cells, may contribute to inflammation and cartilage breakdown in osteoarthritis (OA).

Aged↗

Concentration of interleukin-1 beta in serum and synovial fluid in patients with rheumatoid arthritis and those with osteoarthritis.

The concentration of interleukin-1 beta (IL-1 beta) in serum and synovial fluid of the knee of patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA) was examined using a recently developed radioimmunoassay method. The serum concentration of IL-1 beta was below the detection limit of 0.25 ng/ml in all RA and OA patients. The IL-1 beta concentration in the synovial fluid was higher in RA patients than in OA patients. In RA patients, a significant correlation was demonstrated between the synovial fluid IL-1 beta concentration and the erythrocyte sedimentation rate, C-reactive protein level, synovial fluid white blood cell count and Lansbury index. The synovial fluid IL-1 beta concentration decreased with the reduction of the rheumatoid activity by the medication, but tended to increase or remain high when inflammatory activity of RA could not be adequately controlled. The IL-1 beta concentration, easily determined, shows promise as a new quantitative indicator of rheumatoid activity.

Aged↗

Chemokine receptor CCR4 on CD4+ T cells in juvenile rheumatoid arthritis synovial fluid defines a subset of cells with increased IL-4:IFN-gamma mRNA ratios.

To understand the mechanisms that promote recruitment and survival of T cells within the pediatric inflamed joint, we have studied the expression of CCR4 and CCR5 on synovial fluid T cells and matched peripheral blood samples from juvenile rheumatoid arthritis (JRA) patients using three-color flow cytometric analysis. Thymus- and activation-regulated chemokine and macrophage-derived chemokine, ligands for CCR4, were measured by ELISA in JRA synovial fluid, JRA plasma, adult rheumatoid arthritis synovial fluid, and normal plasma. IL-4 and IFN-gamma mRNA production was assessed in CD4+/CCR4+ and CD4+/CCR4(-) cell subsets. We found accumulations of both CCR4+ and CCR5+ T cells in JRA synovial fluids and a correlation for increased numbers of CCR4+ T cells in samples collected early in the disease process. Thymus- and activation-regulated chemokine was detected in JRA synovial fluid and plasma samples, but not in adult rheumatoid arthritis synovial fluid or control plasma. Macrophage-derived chemokine was present in all samples. CD4+/CCR4+ synovial lymphocytes produced more IL-4 and less IFN-gamma than CD4+/CCR4(-) cells. These findings suggest that CCR4+ T cells in the JRA joint may function early in disease in an anti-inflammatory capacity through the production of type 2 cytokines and may play a role in determining disease phenotype.

Adolescent↗

99mTc-labelled immunoglobulin scintigraphy in arthritis: an analysis of synovial fluid activity.

The distribution of 99mTc-labelled human polyclonal non-specific immunoglobulin G (HIG) in the synovial fluid was studied in 14 patients with rheumatoid and non-rheumatoid arthritides. Analysis included the determination of the total activity per ml synovial fluid 6 h post-injection (p.i.) of the tracer as well as of the protein- and cell-bound fractions. At 6 h p.i., > 60% of the injected dose remained in plasma as protein-bound radioactivity. Values in the synovial fluid ranged between 0.001 and 0.009% of the injected dose per ml. Importantly, the synovial fluid to plasma ratio was consistently < 1 (range: 0.09-0.43), which is in the range of ratios observed for endogenous proteins in vivo. Similar values were obtained in samples of synovial tissue obtained at surgery in two patients. These data are consistent with the hypothesis that labelled HIG accumulates in the extracellular fluid (both within the synovial tissue and fluid) by non-specific mechanisms (such as increased blood pool and capillary permeability) and does not equilibrate with circulating plasma proteins in accordance with basic knowledge of synovial physiology. In addition, it was found that most of the activity remained bound to the proteins in the fluid and that cell-binding occurred to a very low degree that cannot be considered an important mechanism of uptake of this radiolabelled agent in vivo. These results provide the first evidence in an in vivo human setting that radiolabelled HIG accumulates mainly by non-specific mechanisms in inflamed joints.

Arthritis, Rheumatoid↗

[C-reactive protein in inflammatory articular diseases: comparison of concentrations in blood and synovial fluid].

We evaluated the diagnostic value of measuring C-Reactive Protein (CRP) in blood and in synovial fluid for the detection of inflammatory articular diseases in 154 patients. High concentrations of CRP in blood were found in microcrystalin arthritis, polymyalgia rheumatica and Horton's disease. Our results show a good correlation between CRP and erythrocyte sedimentation rate for ankylosing spondylitis (p less than 0.01), systemic lupus erythematosus (p less than 0.01), rheumatoid arthritis (p less than 0.05), polymyalgia rheumatica and Horton's disease (p less than 0.05). The CRP measurement in blood did not separate seropositive versus seronegative rheumatoid arthritis, systemic lupus erythematosus versus rheumatoid arthritis and treated versus non-treated rheumatoid arthritis. There was a good correlation between CRP concentration in blood and in synovial fluid but the concentration was lower in synovial fluid than in blood (p less than 0.01). Then, the CRP measurement in synovial fluid does not have a higher diagnostic value than in blood.

Aged↗

Penetration and bactericidal activity of cefixime in synovial fluid.

The penetration of oral cefixime into the synovial fluids of 16 patients (mean age, 50.6 years) who underwent joint taps for rheumatic noninfectious disorders was examined. The patients were each given a single dose (400 mg) 2 to 24 h prior to the tap. Cefixime concentrations in serum and joint fluid samples were measured by high-performance liquid chromatography, and the bactericidal activities of these fluids against three isolates each of Haemophilus influenzae and Escherichia coli were examined. The highest concentrations in serum and synovial fluid were achieved 4 h following drug intake, the mean values being 2.8 and 2.03 micrograms/ml, respectively. Effective bactericidal activities (bactericidal titer, > 1:2) against E. coli and H. influenzae were demonstrated in serum and joint fluid up to 10 h following oral intake of cefixime. These results suggest that cefixime penetrates well into joint fluid, achieving levels above the MIC for E. coli lasting as long as 10 h and levels above the MIC for H. influenzae lasting up to 24 h after administration. Good bactericidal activity against susceptible bacterial isolates was observed for at least 10 h after dosing.

Adult↗