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PubMed1991

Presence of NAP-1/IL-8 in synovial fluids indicates a possible pathogenic role in rheumatoid arthritis.

The synovial fluid in affected joints of rheumatoid arthritis (RA) patients contains many cells, in numbers strongly correlated with the severity of disease. As the disease worsens and the cell count increases, the polymorphonuclear leucocyte becomes the predominant cell type. Although the inflammatory cytokines interleukin 1 (IL-1) and tumour necrosis factor (TNF) have no direct neutrophil-attractant activity, they are both potent inducers of interleukin 8 (IL-8) in a variety of cell types. Chemotactic attraction of neutrophils is a major activity of IL-8. Examination of a number of synovial fluids showed that significant levels of IL-8 are present in a high proportion of RA cases (10 out of 17), at concentrations directly related to the number of cells in the joint, and to circulating C-reactive protein (CRP) levels. The cytokine is present only at background levels in other diseases accompanied by arthritic manifestations, including systemic lupus erythematosus (SLE) and induced arthritis. The progressive joint destruction seen in all cases where high IL-8 levels were measured, coupled with the neutrophil-rich cell count and the strong correlation between concentration of IL-8 and both serum CRP and cellular influx into the joint, is strongly suggestive of a pathogenic role for IL-8 in RA.

Arthritis, Rheumatoid↗
PubMed2001

Postmortem biochemical examination of synovial fluid--a preliminary study.

Vitreous humor chemistry is used for postmortem analysis since serum values of many components are thought to be reflected in vitreous humor and to be stable for a prolonged postmortem interval (pmi). A similar isolated compartment to vitreous humor is synovial fluid which up to now was hardly used for postmortem chemistry. The aim of the present examination was to compare the values of various analytes in both fluid compartments to get first hints for the reliability of the examination of synovial fluid. Therefore, in 74 cases of sudden death both fluids were taken and analysed for natrium, potassium, calcium, chloride, urea, creatinine, and glucose. The results show that the examination of synovial fluid as compared to vitreous humor is a reliable method to get hints on the premortal metabolic status since most analytes are stable postmortem. The range of all values is comparable in both fluids. The time course of glucose concentrations and, much more important, potassium concentrations is nearly similar. If no vitreous humor is available synovial fluid may be used with all precautions in diagnosis known from vitreous humor.

Calcium↗
PubMedDate not supplied

Plasma and synovial fluid concentrations of nimesulide and its main metabolite after a single or repeated oral administration in patients with knee osteoarthritis.

The aim of this study was to evaluate plasma and synovial fluid concentrations of the non-steroidal anti-inflammatory drug nimesulide and its major metabolite (hydroxynimesulide, M1), after a single 100 mg dose of nimesulide and a repeated (14 day) administration, 100 mg twice a day, in patients with osteoarthritis of the knee and joint effusion. Nimesulide was rapidly absorbed in plasma and distributed in synovial fluid. On day 1, effective concentrations were present 30 min after the first dose and on day 14, the synovial fluid concentration of nimesulide was significantly higher than that measured on day 1; no accumulation was observed in plasma. After 14 days of treatment, both the plasma and synovial fluid concentrations of M1 were significantly higher than those measured on day 1. These data may help to explain the rapid onset of the analgesic effect of nimesulide demonstrated in several clinical conditions, including painful osteoarthritis.

Administration, Oral↗
PubMed2000

Crohn disease arthropathy: antigens in synovial fluid share epitopes with strains of two species of viridans streptococci.

BACKGROUND: There is evidence to suggest that Crohn disease is caused by an immunologic response to an unknown intestinal luminal antigen, probably of bacterial origin. The reported demonstration of yersinia antigen in the synovial fluid of patients with yersinosis therefore prompted a search for bacterial antigens in the synovial fluid of patients with Crohn arthropathy. METHODS: Antisera were raised in rabbits to synovial fluids obtained from seven patients with Crohn arthropathy and from seven 'control' subjects with other forms of arthropathy. These antisera were used to probe sonicates of the bacteria cultured from the gastric juice of patients with gastric Crohn disease. RESULTS: The antisera made from the Crohn synovial fluids, but none of those made from the controls, reacted uniquely with antigens in sonicates of strains of two species of viridans streptococci (Streptococcus parasanguis and an atypical S. oralis) isolated from four of the five patients with gastric Crohn disease. CONCLUSIONS: These findings suggest that the arthropathy of Crohn disease and, possibly, the intestinal disease itself may involve an immunologically mediated inflammatory response to these antigens.

Animals↗
PubMed2001

Effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate on synovial fluid chondroitin sulfate 3B3 and 7D4 epitope in a canine cruciate ligament transection model of osteoarthritis.

OBJECTIVE: To evaluate effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate (CS-G-M) on articular cartilage metabolism in dogs with cranial cruciate ligament (CCL) deficient and reconstructed knees, as reflected by concentrations of synovial fluid 3B3, 7D4 and total sulfated glycosaminoglycan (GAG). METHODS: Sixteen adult dogs that underwent unilateral CCL transection were randomized into four groups. Thereafter, group I (N=3) had a sham CCL reconstruction, group II (N=3) had CS-G-M and sham CCL reconstruction, group III (N=5) had CCL reconstruction, and group IV (N=5) had CS-G-M and CCL reconstruction. Synovial fluid collected at 0, 1, 3 and 5 months was examined by ELISA for 3B3 and 7D4 epitope, and by DMMB assay for total GAG. RESULTS: Synovial fluid from CCL transected knees of CS-G-M treated dogs contained significantly elevated concentrations of 3B3 (P=0.029), 7D4 (P=0.036) and 7D4/GAG (P=0.007) in comparison to controls, in a cross-sectional analysis at 3 months. Furthermore, 7D4 and 7D4/GAG concentrations remained significantly elevated (P=0.012) in CCL transected knees of CS-G-M treated dogs over the 5 month period. However, when epitope concentrations were expressed as a ratio of CCL-transected to contralateral non-operated knee, treatment effect of CS-G-M was no longer significant. Reconstruction of the CCL had no significant effect on synovial fluid epitope. CONCLUSIONS: Administration of CS-G-M was associated with altered concentrations of 3B3 and 7D4 epitope in synovial fluid, suggesting that these compounds may act to modulate articular cartilage matrix metabolism in vivo.

Administration, Oral↗
PubMed2000

Reduced expression of the complement receptor type 2 (CR2, CD21) by synovial fluid B and T lymphocytes.

The expression of CR2 (CD21) by synovial B and T lymphocytes of patients suffering from various forms of arthritis was analysed with cytofluorometry and with reverse transcriptase-polymerase chain reaction. CR2 (CD21) cell surface protein was detected in normal quantities on peripheral B cells, but was almost absent on synovial B lymphocytes of the same patients. This reduction was most severe in patients with rheumatoid arthritis, but also observed in all other cases. CR2 (CD21) did not reappear after in vitro culture. CR2 (CD21) mRNA was also strongly reduced in synovial B and T lymphocytes. Synovial fluid B lymphocytes were larger than peripheral blood B lymphocytes, while T cells from the same patients showed no size differences. We conclude that synovial fluid B lymphocytes have undergone an irreversible step towards terminal differentiation. The presence or absence of CR2 (CD21) mRNA in peripheral versus synovial T cells indicates that CR2 (CD21) is also differentially expressed by T lymphocytes.

Adult↗
PubMed1987

Collagenase-like (CL) peptidase activity in synovial fluid from patients with rheumatoid arthritis.

We found the presence of collagenase-like (CL) peptidase in synovial fluid by a highly sensitive fluorescence assay using (succinyl-Gly-Pro-Leu-Gly-Pro)-4-methyl-coumaryl-7-amide (Suc-GPLGP-MCA) as a substrate. Suc-GPLGP-MCA is hydrolyzed at the Leu-Gly bond by CL-peptidase. The CL-peptidase activity in synovial fluid was significantly higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA) and in arthropathy-free controls. No significant difference in CL-peptidase activity in synovial fluid was found between patients with OA and arthropathy-free controls.

Arthritis, Rheumatoid↗
PubMed2000

Synovial fluid from loose hip arthroplasties inhibits human osteoblasts.

Aseptic loosening of prosthetic components in patients who have undergone total hip arthroplasty is a major clinical problem. Earlier studies on this topic have focused mainly on different aspects of bone resorption. The current study investigated the influence of synovial fluid from patients who underwent revision surgery because of aseptic loosening and synovial fluid from patients with osteoarthritis on the proliferation of primary cultures of human osteoblasts. Incubation of cells with 10% synovial fluid from patients who had revision surgery significantly inhibited [3H]thymidine incorporation into deoxyribonucleic acid in human osteoblasts compared with control conditions, whereas 10% synovial fluid from patients with osteoarthritis had a significant stimulatory effect. These findings correlate well with clinical features seen in these diseases, such as increased net bone resorption around the prosthesis in patients with loosening, and increased periarticular bone formation in patients with osteoarthritis.

Aged↗
PubMed1996

Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation.

Chronic immune responses and inflammatory reactions in rheumatoid arthritis (RA) often cause severe destruction of cartilage and bone, but its mechanism is still a matter of controversy. We reported that interleukin-6 (IL-6) alone does not induce osteoclast formation, but soluble interleukin-6 receptors (sIL-6R) triggered the formation in the presence of IL-6 in cocultures of murine osteoblastic cells and bone marrow cells. In this study, we examined the involvement of sIL-6R and IL-6 in joint destruction in patients with RA. Although the frequency of patients having osteoclast-like multinucleated cells in synovium derived from the knee joint was not significantly different between RA (65%) and osteoarthritis (OA) patients (43%), the number of osteoclast-like cells found in the synovium was greater in the former than in the latter. Multinucleated cells obtained from RA synovium expressed the osteoclast-specific phenotype such as tartrate-resistant acid phosphatase, carbonic anhydrase II, vacuolar proton-ATPase and vitronectin receptors at similar levels to those from a human giant cell tumor of bone. The concentration of both IL-6 and sIL-6R was significantly higher in the synovial fluids from patients with RA than with OA. The concentration of IL-6 and sIL-6R correlated well with the roentgenologic grades of joint destruction. Dose-response curves for human IL-6 and human sIL-6R in inducing osteoclast-like cell formation in cocultures indicated that the RA synovial fluids contained sufficient IL-6 and sIL-6R to induce osteoclastogenesis. When synovial fluids from RA and OA patients were added to the cocultures, some of the RA synovial fluids containing high levels of IL-6 and sIL-6R stimulated osteoclast-like cell formation, which was strikingly inhibited by adding anti-IL-6R antibody simultaneously. These results suggest that IL-6 in the RA synovial fluids is at least in part responsible for joint destruction in the presence of sIL-6R through osteoclastogenesis.

Acid Phosphatase↗
PubMed1996

Serum YKL-40 levels in healthy children and adults. Comparison with serum and synovial fluid levels of YKL-40 in patients with osteoarthritis or trauma of the knee joint.

YKL-40 is a recently discovered human glycoprotein which is related in amino acid sequence to the chitinase protein family. YKL-40 is a major secretory protein of human chondrocytes and synoviocytes, and could play a role in tissue remodelling. The aim of the study was to establish the serum YKL-40 level in normal subjects and to evaluate serum YKL-40 as a marker for osteoarthritis. Serum YKL-40 was 80 micrograms/l in healthy children (n = 476) and 102 micrograms/l in healthy adults (n = 260). No age or sex differences were found in serum YKL-40 in subjects younger than 70 yr, but thereafter serum YKL-40 increased significantly. Patients with late-stage osteoarthritis of the knee (n = 37) had significantly higher serum YKL-40 (1.5-fold; P < 0.01) compared to healthy age-matched subjects, whereas patients with early-stage osteoarthritis of the knee or recent torn cruciate ligaments or menisci did not have elevated serum YKL-40. The level of YKL-40 in serum and synovial fluid correlated significantly, and 10-fold higher values were found in synovial fluid. YKL-40 levels in serum and synovial fluid of patients with acute severe synovial inflammation were significantly higher (P < 0.05-P < 0.001) than those in patients with no, light or moderate synovitis of the knee joint. Furthermore, YKL-40 correlated significantly (P < 0.01) with the amino-terminal propeptide of type III procollagen, but not with serum C-reactive protein. Our data indicate that YKL-40 in synovial fluid and serum may reflect human articular cartilage degradation and the degree of synovial inflammation in the knee joint.

Adipokines↗
PubMed2003

Automated counting of white blood cells in synovial fluid.

OBJECTIVES: To evaluate the performance of automated leucocyte (white blood cell; WBC) counting by comparison with manual counting. METHODS: The number of WBC was determined in heparinized synovial fluid samples by the use of (i) a standard urine cytometer (Kova) and a microscope (reference method) and (ii) a haematology analyser (Sysmex XE-2100; WBC/BASO and DIFF channels). Imprecision within and between days was determined by replicate analysis of a low (level A; WBC approximately 0.560 x 10(9)/l) and a high (level B; WBC approximately 1.081 x 10(9)/l) dedicated synovial fluid control (Quantimetrix). RESULTS: The WBC count of the DIFF channel was highly correlated with the WBC count of the microscopic reference method (r = 0.99; WBC analyser = 0.870 x WBC reference method + 0.413). In contrast, no agreement existed between WBC counts generated by the WBC/BASO channel of the analyser and the reference method (r = 0.52; WBC analyser = 0.008 x WBC reference method + 0.079). Within-day imprecision (4-7%) and between-day imprecision (10%) of the haematology analyser were smaller than the within-day imprecision (12%) and the between-day imprecision (20-22%) of the manual reference method. For manual counting, inter-observer coefficients of variation were 35.9% (control level A) and 21.0% (control level B). CONCLUSIONS: The WBC count in synovial fluid can be reliably determined using the DIFF channel of the Sysmex XE-2100. Automated counting of WBC in synovial fluid offers more precise and faster results than manual counting.

Arthritis↗
PubMedDate not supplied

Effects of synovial fluid on fibroblasts in tissue culture.

The ability of the torn anterior cruciate ligament of the knee to heal is unpredictable, despite early surgical repair. A popular explanation has been that synovial fluid inhibits ligament healing. Other variables of ligament healing could reside with the fibroblasts, themselves, from different ligaments. With the use of tissue culture techniques, populations of fibroblasts were cultured from human anterior cruciate ligaments, deep and superficial medial collateral ligaments of the knee. Growth of fibroblasts from the anterior cruciate ligament was always diminished when exposed to synovial fluid and, on the average, plating efficiency was reduced by 46% when the culture medium contained synovial fluid. Growth rates demonstrated that fibroblasts from the superficial medial collateral ligament grew an average of 35% more than the others. Information gained from this study provides some data to explain the clinical frustration of the torn anterior cruciate ligament. The combination of synovial fluid inhibition of cell proliferation and the variable growth rates of fibroblasts, may explain the unsatisfactory healing of cruciate ligaments.

Cell Count↗
PubMed1989

1H nuclear magnetic resonance investigation of synovial fluid components in osteoarthritis, rheumatoid arthritis and traumatic effusions.

The levels of a range of components were measured by 1H nuclear magnetic resonance (1H NMR) in samples of synovial fluid taken from three groups of patients: 10 with osteoarthritis (OA), 18 with rheumatoid arthritis (RA), and 11 with traumatic effusions. A large number of low molecular weight species were measured simultaneously in addition to triglycerides and glycoproteins. Large variations were found between individuals in any one disease group, and there was no measurable correlation between disease state and levels of any low molecular weight component. However, patients with traumatic effusions had high levels of saturated triglycerides, while those with OA had low levels. The chain length of the triglycerides found in OA synovial fluid appears to be shorter than that for the other groups. In RA the composition of triglycerides appears normal, while the overall level is slightly above normal. In a separate study, serial samples of synovial fluid drawn from the knees of two arthritic patients were examined, and the concentrations of glycoprotein, triglycerides and creatinine were found to show a reasonable correlation with each other and with systemic measures of disease activity. These data suggest the potential of synovial fluid triglycerides and creatinine as inflammatory markers.

Arthritis, Rheumatoid↗
PubMed1978

Synovial fluid eosinophilia following arthrography.

A patient recovering from an acute gouty attack developed inflammation and eosinophilia of the synovial fluid following arthrography of the gouty joint. There was no evidence of systemic allergy to the contrast agent used. It is postulated that non-immune mechanisms were involved in the accumulation of eosinophils. An additional one of six synovial fluids obtained after arthrography contained 24% eosinophils. A review of the literature emphasizes the infrequency with which eosinophils are observed in synovial fluid.

Diatrizoate↗
PubMed2005

Fibroblast-like synovial cells derived from synovial fluid.

OBJECTIVE: To obtain fibroblast-like synovial cells (FLS) from synovial fluid (SF). METHODS: SF aspirated from joints of patients with rheumatoid arthritis (RA), other types of inflammatory arthritis, and osteoarthritis (OA) was centrifuged and the resulting cell pellet resuspended in growth medium. After 2 days, nonadherent cells were removed. FLS were also cultured from surgical specimens of synovial tissue (td-FLS). Phenotype characterization of fluid derived FLS (fd-FLS) was accomplished by flow cytometry and immunohistochemistry staining. Tumor necrosis factor-alpha (TNF-alpha) induced interleukin 6 (IL-6), IL-8, and cyclooxygenase 2 (COX-2) mRNA levels were assessed. RESULTS: Second and later passage fd-FLS exhibited uniform fibroblast-like morphology. Fd-FLS and td-FLS expressed a similar profile of cell surface antigens including the fibroblast marker Thy-1. Less than 2% of either cell type expressed surface markers characteristic of dendritic cells, phagocytic cells, T cells, or leukocytes. Immunohistochemistry staining revealed the presence of fibroblast products prolyl-4 hydroxylase, procollagen I, and procollagen III in both culture types. TNF-a induced increases in IL-6, IL-8, and COX-2 mRNA were suppressed by dexamethasone in both fd-FLS and td-FLS. CONCLUSION: FLS can be cultured from SF. The fibroblast phenotype was confirmed by analysis of surface antigens and intracellular proteins. Inflammatory mediators produced after stimulation of both fd-FLS and td-FLS were suppressed by dexamethasone. In addition to providing a more accessible source of FLS, fd-FLS may also facilitate study of synovial cells in early RA when tissue specimens are not readily available.

Arthritis↗
PubMed1994

Increased usage of V beta 2 and V beta 6 in rheumatoid synovial fluid T cells.

OBJECTIVE: To determine if the T cell antigen receptor V beta usage of unstimulated rheumatoid arthritis (RA) synovial fluid (SF) T cells is biased compared with those in peripheral blood (PB). METHODS: Freshly isolated, matched synovial fluid and peripheral blood T cells were analyzed for V beta gene expression using quantitative polymerase chain reaction (PCR) methods. Ten synovial fluid samples from the knees of 7 patients with RA were studied. The PCR assay used 26 V beta primers with a constant region C beta primer, and 2 C alpha primers that co-amplified a product that served as an internal standard. Cycle number and complementary DNA content were controlled to ensure the linear accumulation of PCR products. Labeled products were separated on 10% polyacrylamide gels and counted with a Betascope blot analyzer. RESULTS: There were consistent differences between the V beta gene usage of SF and PB T cells directly isolated from patients with RA, regardless of HLA-DR haplotype. In all synovial specimens, V beta 2 was increased relative to the peripheral blood, while V beta 13.1 and V beta 13.2 were decreased. V beta 6 and V beta 21 were increased in 9 of the 10 synovial samples. Analyses of bilateral SF specimens from 2 subjects and serial specimens from the same knee of 1 subject revealed virtually identical patterns in each patient. The SF V beta bias was not solely due to differences in the proportion of CD4+ and CD8+ cells, because the CD4:CD8 ratios in SF and PB were similar. However, V beta gene usage of separated CD4+ and CD8+ synovial T cells showed that V beta 2 and V beta 6 were more highly expressed on CD4 cells. CONCLUSION: Freshly isolated synovial T cells from inflamed (not end-stage) knees of patients with RA have a remarkably consistent biased V beta gene usage compared with PB T cells. V beta 2 and V beta 6 are uniformly increased, and this increase is primarily in CD4+ T cells. The same V beta bias in the SF T cells of several RA patients suggests that shared antigens may be stimulating the T cell response.

Adult↗
PubMed1992

Interleukin-8 in inflammatory rheumatic diseases: synovial fluid levels, relation to rheumatoid factors, production by mononuclear cells, and effects of gold sodium thiomalate and methotrexate.

The content of interleukin-8 (IL-8) in the synovial fluid and its production by blood and synovial fluid mononuclear cells (PBMC and SFMC) was compared in rheumatoid arthritis (RA) and various other inflammatory rheumatic disorders. The study included 125 patients and 20 healthy individuals. The highest concentrations of IL-8 were found in the synovial fluids and culture supernatants of PBMC and SFMC from patients with seropositive RA. Only PBMC from seropositive patients, and not from other rheumatic diseases, exhibited significant spontaneous release of IL-8 that correlated with serum IgM rheumatoid factor titers. Gold sodium thiomalate (GST) and methotrexate (MTX) inhibited the spontaneous and stimulated IL-8 production by PBMC by 55-86% at 50 and 10 micrograms/ml, respectively. Two main conclusions were drawn: (1) rheumatoid factors appeared to be a major cause of enhanced IL-8 production in seropositive RA, and (2) inhibition of IL-8-mediated neutrophil migration and activation could be part of the mechanism of action of GST and MTX.

Anti-Inflammatory Agents↗
PubMed1978

Subclasses IgA1 and IgA2 in serum and synovial fluid in rheumatoid arthritis and reactive synovitis of local origin.

Subclasses IgA1 and IgA2 in serum were examined in 40 patients (28 cases of rheumatoid arthritis and 12 cases of reactive synovitis of local origin) and also in synovial fluid of the knee joint in 17 of these patients. The levels of IgA1 and IgA2 in serum were statistically significantly higher than in synovial fluid in both groups of patients (P = 0.0237--0.0018), but significant correlations between serum and synovial fluid for IgA1 (R = 0.8855, P = 0.0010) and for IgA2 (r = 0.7630, P = 0.0124) were found only in cases of rheumatoid arthritis. A percentage evaluation revealed a significant disproportion (P = 0.0028) in favour of IgA1 in synovial fluid during rheumatoid arthritis. The analysis of proportions of IgA subclasses and rheumatoid factor has shown no significant relationships.

Adult↗