scholarly journals Evaluation of the degree of clinical rheumatoid arthritis activity based on the concentrations of cytokines TNF-alpha, IL-12, IL-15, and IL-18 in serum and synovial fluid

2006 ◽  
Vol 63 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Ljiljana Petrovic-Rackov

Bacground/Aim. Experimental in vitro and in vivo investigations in a mouse model have proved that TNF-alpha, IL-12, IL- 15 and IL-18 participate in the pathogenesis of erosive inflammatory arthritis. The aim of this research was to determine the clinical significance of cytokines in the evaluation of the activity of rheumatoid arthritis (RA). Methods. Inside a 4-year period we followed-up 64 patients with RA as newly occurred or in the phase of worsening. We observed the clinical manifestation of the disease upon wluch we divided the patients in to 3 groups: the patients with low active RA, patients with moderate active RA, and the patients with wild active RA. The control group (n = 25 patients) included the patients with osteoarthrosis (OA), and arthritis of the knee. In the samples of serum of all of the patients the concentrating of cytokines TNF-alpha, IL-12, IL-15, and IL-18 were determined using the immunoenzymatic methods in mice for human interleukines. By comparing the concentrations in 30 patients with the high, 14 patients with moderate, and 20 patients with the mild activity of RA it was determined that the patients with the high degree of the disease activity, had significantly high (p < 0.01; p < 0.05) concentrations of the examined cytokines in blood and synovial fluid as compared to the patients with the moderate and mild active disease. There was a relationship (p < 0.01) between the concentrations of cytokines in blood and synovial fluid with the quantity of the Disease Activity Score in 28 joints. Conclusions. Cytokines concentrations could be good indicators of the degree of the general activity of RA. This research could contribute to the interpretation of insufficiently well known views of the pathogenesis role and significance of citokines in an active disease.

2005 ◽  
Vol 58 (5-6) ◽  
pp. 245-251 ◽  
Author(s):  
Ljiljana Petrovic-Rackov

The aim of this research was to determine the clinical significance of tumor necrosis factor-alpha (TNF-alpha), IL-12, IL-15 and IL-18 in evaluation of the activity of rheumatoid arthritis. Cytokine concentrations in serum samples and synovial fluid were measured by immnnoenzymatic methods using kits for human interleukins and the Disease Activity Score 28 in 64 patients with active disease. The control group consisted of 25 subjects with arthritis of the knee and osteoarthrosis. Patients with rheumatoid arthritis have significantly high (p<0.01) concentrations of examined cytokines in relation to patients with osteoarthritis. By comparing concentrations in 30 patients with high, 14 patients with moderate and 20 patients with mild activity of rheumatoid arthritis, it was established that patients with high degree of disease activity have significantly high (p<0.01; p<0.05) concentrations of examined cytokines in the blood and synovial fluid in relation to patients with moderate and mild disease. We have concluded that cytokine concentrations are good indicators of the degree of rheumatoid arthritis activity. This research is a contribution to understanding the insufficiently known pathogenetic mechanisms of cytokines, especially IL-18, in active disease. .


2004 ◽  
Vol 23 (4) ◽  
pp. 375-380 ◽  
Author(s):  
Ljiljana Petrovic-Rackov ◽  
Nada Pejnovic ◽  
Zoran Mijuskovic ◽  
Gordana Ercegovic

The aim of the research is to determine the clinical significance of cytokines TNF-alpha, IL-12, IL-15 and IL-18 in evaluation of the activity of rheumatoid arthritis (RA). By comparing the concentrations in 30 patients with high, 14 patients with moderate and 20 patients with mild activity of RA it is established that the patients with high degree of disease activity, have significantly high (p<0.01; p<0.05) concentrations of examined cytokines and rheumatoid factor in blood and synovial fluid as well as C-reactive protein in serum in relation to patients with moderate and mild active disease. We have concluded that the cytokines concentrations can be good indicators of the degree of the general activity of RA. This research can contribute to interpretation of insufficiently well known views of pathogenesis role of cytokines in active disease.


2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.


2020 ◽  
Vol 29 (3) ◽  
pp. 47-51
Author(s):  
Dalia A. Elsayed ◽  
Samy E. Egila ◽  
Yaser A. Abd El-Hammed ◽  
Rasha A. Elsayed ◽  
Noha Hosni Ibrahim

inflammatory autoimmune disease with a frequency of 0.5–1.0% between the adult population of developed countries. It is marked by chronic inflammation of synovial tissue and accompianed by damage of the articular cartilage and adjecent bone, leading to substantial disability. Objectives: The aim of this study is to determine serum and synovial fluid levels of calprotectin in rheumatoid arthritis patients and to determine its relation with disease activity and severity. Methodology: This study was carried out on 40 rheumatoid arthritis patients who were admitted to Rheumatology, Rehabilitation and Physical Medicine Outpatient’ clinic and Inpatient Department of Benha University Hospital .Also Thirty age and sex matched( 28 females and 2 males ) apparently healthy volunteers were included in the study as a control group . All patients were assessed by full medical history, clinical examination, functional assessment, laboratory investigations including CBC, ESR ,CRP, liver functions, RF, Anticcp antibody, and Xrays were done to both hands. Serum and synovial levels of calprotectien were measured using the ELISA technique. Results: Serum levels of calprotectien were significantly higher in RA patients than healthy subjects [p<0.001], also there was a highly statistically significant increase in the mean synovial fluid calprotectin levels than mean serum calprotectien levels [p<0.001]. Local and systemic levels of calprotectin correlate with clinical, immunological and instrumental assessments of disease activity and the inflammatory degree of the joint. Conclusion: Calprotectin could be used as a new biomarker for monitoring the disease activity and severity of RA. Larger sets are needed to confirm the diagnostic and prognostic accuracy of calprotectin in RA


2009 ◽  
Vol 28 (3) ◽  
pp. 166-171 ◽  
Author(s):  
Zoran Mijušković ◽  
Ljiljana Rackov ◽  
Janko Pejović ◽  
Sandra Živanović ◽  
Jelica Stojanović ◽  
...  

Immune Complexes and Complement in Serum and Synovial Fluid of Rheumatoid Arthritis PatientsRheumatoid arthritis (RA) is predominantly an intraarticular inflammatory and autoimmune disease that involves different autoantibodies and effector mechanisms. The aim of the study was to determine the utility of Circulating Immune Complexes (CIC) and complement components (C3c, C4) as possible markers for the disease activity in laboratory diagnostics. In a cross-section study 59 patients, according to the clinical criteria, were categorized into two groups: group with moderate (MA, n=24), and group with severe activity (SA, n=35) of RA. The concentration of CIC, C3c and C4 in sera (S) and synovial fluids (SF) was examined by an immunonephelometric method in both groups and compared with values in the control group (n=15) of patients with lesions of the menisci. Obtained results showed that there was no statistical significance in the values of C3c and C4, in both biological fluids, among all tested groups. Significant differences were found in the levels of CIC in both fluids, while testing the parameters (× ± SD, IU/mL) in the sera of groups with SA and MA of RA: 7.43 ± 13.40; 3.01 ± 2.92 (p<0.05) and SF: 13.47 ± 21.1, 5.33 ± 7.53 (p<0.001), respectively. These differences were higher between the group with SA and CG. Results for the concentrations of CIC were significantly higher in SF compared to sera: in the RA group with SA by 77% and group with MA by about 82%. These data could provide a confirmation of the hypothesis about local, intraarticular autoantibodies and subsequent CIC production. It can be concluded that the examination of CIC concentration in serum, and where it is possible in SF, is a useful marker of disease activity in RA patients, in contrast to the tested components of the complement. This statement does not exclude their consumption within immune effector mechanisms, but elicits the possibility that lower molecular fragments (C3d, C4d), as well as the novel activation products, could be better disease activity markers in RA patients.


2017 ◽  
Vol 74 (10) ◽  
pp. 940-946 ◽  
Author(s):  
Nela Zivkovic ◽  
Boris Djindjic ◽  
Sonja Stojanovic ◽  
Ivana Krstic ◽  
Ivana Ciric ◽  
...  

The essence of rheumatoid arthritis (RA) pathogenesis is inflammation, modification of immune system and cell damage. 5'-nucleotidase (5'-NT) and adenosine deaminase (ADA) have a significant role in the process of inflammation-caused tissue damage. The aim of the paper is to define 5'-nucleotidase and adenosine deaminase activity in serum of patients with rheumatoid arthritis treated with Methotrexate and patients with rheumatoid arthritis who have not been treated with Methotrexate, as well as to determine correlation between the enzymes and disease activity. The research included 160 patients suffering from rheumatoid arthritis, 60 of which have not been treated with Methotrexate (age 56,8; 68,3% female) and 100 patients treated with Methotrexate (age 59,8; 88% female), as well as 60 healthy controls (age 58,8; 66,6% female). Patients suffering from chronic inflammatory diseases, chronic respiratory, cardiac and kidney insufficiency, severe acute diseases and other diseases which might modify inflammatory response were not included in the research. There was no statistically significant difference in 5'-NT values among groups. ADA values were significantly different in all tested groups. Post Hoc analysis (Dunnett T3 test) showed that ADA activity in RA groups were significantly higher as compared to control group (p<0.001), and that ADA in RA group with MTX was significantly smaller as compared to RA group without MTX (p<0.001). There is not significant correlation between the disease activity and activities of tested enzymes. We concluded that adenosine deaminase activity was increased in patients with rheumatoid arthritis, as well as that the application of Methotrexate led to the decrease of this enzyme in the serum of patients with rheumatoid arthritis. Activity of 5'-nucleotidase is not increased in patients with rheumatoid arthritis and did not depend on Methotrexate treatment. Serum adenosine deaminase and 5'-nucleotidase were not good indicators of rheumatoid arthritis activity.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1349.1-1349
Author(s):  
D. Køster ◽  
J. H. Egedal ◽  
M. Hvid ◽  
M. R. Jakobsen ◽  
U. Müller-Ladner ◽  
...  

Background:Fibroblast-like synoviocytes (FLS) are central cellular components in persistent inflammatory joint diseases such as rheumatoid arthritis (RA). Pathological subsets of FLS have been identified from synovial tissue. However, the synovial tissue obtained from arthroplasty procedures is acquired at late disease stages and the cellular yield obtained from synovial tissue biopsies is fairly low. Collectively, challenging the robustness of human RAin vivoandin vitromodels. FLS obtained from the synovial fluid (SF-FLS) are proposed as an alternative source of FLS, but a detailed phenotypical and functional characterization of FLS subsets from the synovial fluid has not been performed.Objectives:The aim of this study was to determine the phenotypical and functional characteristics of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis.Methods:In the present study, paired peripheral blood mononuclear cells (PBMC) and SF-FLS from patients with RA were obtained (n=7). FLS were isolated from the synovial fluid by a strict trypsinization protocol1and their cellular characteristics and functionality were evaluated at passage 4. Monocultures (SF-FLS) and autologous co-cultures (SF-FLS and PBMC) were established from five patients with RA and subsequently evaluated by flow cytometry, Western blotting and multiplex immunoassays. Human cartilage-sponges (n=3) with SF-FLS and without SF-FLS (n=3) were co-implanted subcutaneously in SCID mice (n=15), mice with only cell-free human cartilage-sponges were used as controls (n=12). After 45 days, the implants were evaluated using stained sections to determine the SF-FLS invasion score based on perichondrocytic cartilage degradation. Data are expressed as median (25-75 percentile). P-values <0.05 were considered statistically significant.Results:The homogeneous subpopulations of FLS, isolated from the synovial fluid, were negative for CD34 and CD45 [98.9%, (97.5-99.7]) and positive for Thy-1 and PDPN [94.6%, (79.9-97.4]). Without stimulation, RA SF-FLS showed high and comparable levels of NFκB related pathway proteins and secreted multiple pro-inflammatory cytokines and chemokines dominated by IL-6 [2648 pg/mL, (1327-6116)] and MCP-1 [2458 pg/mL, (692-8719)]. SF-FLS increased their ICAM-1 and HLA-DR expression after encountering autologous PBMCs (p<0.01), (p<0.05). Further, SF-FLS and PBMC interacted synergistically in a co-culture model of RA and significantly increasing the secretion of several cytokines (IL-1β, IL-2, IL-6, (p<0.01)) and a chemokine (MCP-1, (p<0.01)). The invasion score of the human SF-FLSin vivowas at primary site, [1.6, (1.3-1.7)] and contralateral implantation site [1.5, (1.1-2.2)]. The invasion score of the human SF-FLS-containing implants both at primary and contralateral site were significantly higher compared with cartilage-sponges evaluated from SF-FLS-free control mice (p<0001).Conclusion:This phenotypical and functional characterization of SF-FLS, acquired and activated at the site of pathology, lays a foundation for establishingin vivoandin vitroFLS models. These FLS models will be beneficial in our understanding of the role of this cellular subset in arthritis and for characterization of drugs specifically targeting this pathological RA FLS subset.References:[1]Nielsen M. A. et al. Responses to Cytokine Inhibitors Associated with Cellular Composition in Models of Immune-Mediated Inflammatory Arthritis. ACR Open Rheumatology, 2(1):3-10.http://doi.org/10.1002/acr2.11094Disclosure of Interests:Ditte Køster: None declared, Johanne Hovgaard Egedal: None declared, Malene Hvid: None declared, Martin Roelsgaard Jakobsen: None declared, Ulf Müller-Ladner Speakers bureau: Biogen, Bent Deleuran: None declared, Tue Wenzel Kragstrup Shareholder of: iBio Tech ApS, Consultant of: Bristol-Myers Squibb, Speakers bureau: TWK has engaged in educational activities talking about immunology in rheumatic diseases receiving speaking fees from Pfizer, Bristol-Myers Squibb, Eli Lilly, Novartis, and UCB., Elena Neumann: None declared, Morten Aagaard Nielsen: None declared


2020 ◽  
Author(s):  
Jing Wu ◽  
Qiang Li ◽  
Jia-Xin Deng ◽  
Jin-Jun Zhao ◽  
Qing-Hong Yu

Abstract Background: Interleukin-33 (IL-33) is a member of the IL-1 family of cytokines whose role remains controversial in rheumatoid arthritis (RA), because no clear conclusion has been established regarding the relationship between IL-33 and other cytokines and chemokines. The present study was conducted to evaluate the correlation of IL-33 with other cytokines and chemokines in serum and the synovia, and to explore the nature of the relationship.Results: IL-33 was found to exhibit an inverted-U-shaped correlation with multiple cytokines and chemokines in synovial fluid, including IL-6, IL-1β, CXCL8 (IL-8), CXCL9 (MIG) and CXCL10 (IP-10), but not in serum. Moreover, in vitro experiments confirmed that IL-33 also exhibits U-type dose-dependent regulation of FLS function.Conclusions: IL-33 exhibit an inverted-U-shaped correlation with multiple cytokines and chemokines in synovial fluid of RA patients. IL-33 affects the secretion of cytokines and chemokines in the synovium in a U-type dose-dependent relationship.


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