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ID PMID Title PublicationDate abstract
15144129 MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in patients with rheumatoid arthritis and psoriatic 2004 May OBJECTIVE: Rheumatoid arthritis (RA) and psoriatic arthritis (PA) are both chronic rheumatic inflammatory diseases characterized by disruption of the extra-cellular matrix (ECM) protein of the cartilage, likely induced by proteolytic enzymes such as matrix metalloproteases (MMPs). The goal of this study was to quantify the expression of MMPs such as MMP-2 and MMP-9, and their physiological tissue inhibitors TIMP-2 and TIMP-1, respectively, in serum and synovial fluid. METHODS: Serum and synovial fluid from 24 RA patients and 17 PA patients were studied to determine the levels of MMP-2 and MMP-9 proteolytic activity using a modified gelatin zymography procedure. TIMP-1 and TIMP-2 were measured by a commercially available ELISA kit. RESULTS: Our results show that MMP-2 was detected in the latent form only, while MMP-9 was present in latent and active form. Both gelatinases were more concentrated in synovial fluid than in serum, and TIMP-1 and TIMP-2 concentrations were also more elevated in synovial fluid than in serum. CONCLUSIONS: To investigate the remodelling of cartilage ECM proteins, the evaluation of synovial fluid concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 is more reliable than that determined in serum. In view of these data, MMPs inhibitors might represent a possible target for new therapies delivered directly in the joint space.
15349730 [Possibilities of whole-body MRI for investigating musculoskeletal diseases]. 2004 Sep This contribution outlines possibilities and limitations of whole-body MRI for investigating musculoskeletal diseases. Benefits and drawbacks of the novel whole-body MRI technology are discussed and a possible whole-body MRI sequence protocol for musculoskeletal examinations is proposed. Muscle, joint and bone diseases are discussed in which the application of whole-body MRI may be of advantage. Particularly, polymyositis, muscledystrophy, rheumatoid arthritis, spondylitis ancylosans, multiple trauma, skeletal metastases, multiple myeloma and malignant lymphoma are mentioned. Whole-body MRI opens new advantages for the examination of multifocal musculoskeletal diseases. The clinical benefit of this method for particular diseases has to be evaluated in further studies, however.
15338495 Utility of red amsler grid screening in a rheumatology clinic. 2004 Sep OBJECTIVE: To ascertain the false positive rate of red Amsler grid screening in an outpatient rheumatologic setting. METHODS: Red Amsler grid screening was performed on 170 consecutive patients presenting with rheumatoid arthritis or systemic lupus erythematosus. Patients with abnormal screening results were referred for ophthalmologic evaluation and formal visual field testing. RESULTS: Nineteen patients identified scotomata on red Amsler grid. Despite numerous recall attempts, only 9 of the 19 patients with scotomata presented for ophthalmologic evaluation. The positive predictive value was 5-58%. Roughly 6-11% of all patients screened had a false positive screening test. CONCLUSION: While red Amsler grid screening may allow rheumatologists to identify patients who are more likely to have hydroxychloroquine ocular toxicity, an abnormal red Amsler grid screening is in itself an unreliable predictor of toxicity.
12170875 Neutrophilic dermatoses. 2002 Jul The neutrophilic dermatoses are a group of related cutaneous disorders that frequently have systemic manifestations or associations. While there are distinct clinical differences in the classical lesions of these disorders, there are many patients who have overlapping features. In addition, the associated systemic manifestations or associated diseases are often similar among these disorders. Finally, the management of these disorders with the frequent use of corticosteroids and nonsteroidal immunosuppressive or immunomodulatory agents is common.
11792887 Prediction of successful application for disability benefits for people with arthritis usi 2002 Jan BACKGROUND: Many eligible people with arthritis do not receive disability benefits. Application forms are lengthy and complex, and doctors and nurses are often unsure which patients would qualify. AIM: To investigate how severe disability on the Health Assessment Questionnaire (HAQ) relates to successful application for disability benefits by people with osteoarthritis (OA) and rheumatoid arthritis (RA). METHOD: RA patients attending a hospital out-patient rheumatology clinic and patients with OA or RA in two general practices completed an HAQ and were asked about receipt of disability benefits. Those scoring 2 or more on the HAQ (severe disability) and not in receipt of benefits were offered professional help to complete applications for Disability Living Allowance (DLA) or Attendance Allowance (AA). RESULTS: Eighty per cent of patients with an HAQ score of 2 or more were already in receipt of benefits. Seventy-nine per cent of the new applicants applied successfully, the average benefit being in excess of 2580 pounds per annum. CONCLUSION: This initial study suggests that people who score 2 or more on the HAQ should be encouraged to apply for disability benefits. A test of the generalizability of these findings and the success rate associated with lower HAQ scores should be undertaken.
15160322 [Celecoxib in the symptomatic treatment of active osteo- or rheumatoid arthritis. Results 2004 May 21 BACKGROUND AND OBJECTIVE: The introduction of cyclooxygenase (COX)-2 selective drugs now offers physicians the possibility of a adequate analgesic and anti-inflammatory therapy. Drug induced side effects typically associated with NSAIDs are reduced. Using a post-marketing surveillance study (PSS) efficacy and tolerability of the COX-2-selective drug Celecoxib was evaluated. Patients were not restricted in the use of other medication. PATIENTS AND METHODS: By means of a prospective, non-intervening PSS patients mainly suffering from musculoskeletal conditions such as osteoarthritis (70.5 %) or rheumatoid arthritis (19.6 %) were examined by about 12,000 physicians. The median observation period was almost 5 weeks. RESULTS: In total 70236 patients (42 % males, 58 % females, mean age 60.3 years) were assessed. About 87 % of the patients were adequately treated with a daily dose of 200 mg. The tolerability of the treatment was judged to be "good" to "very good" by the physicians in 97 % and by the patients in 96 % of the cases. The overall incidence of undesirable events (UE) with or without potential causal relationship with the study medication was 2.8 % (1,955 patients), severe UEs manifesting in 0.3 % (223) of all patients. CONCLUSIONS: Overall, the PSS confirms the evident subjective efficacy and tolerability by both the physician's and the patient's overall assessment.
15280423 Suppressor T cells in human diseases. 2004 Aug 2 Although central and peripheral tolerance are important for the regulation of human immune responses to self- and microbial antigens, an important role of suppressor CD4(+) CD25(+) T cells is suggested from the recent investigations of human autoimmune diseases and HIV. These new data provide increasing evidence that altered function of CD4(+) CD25(+) T cells may be an important factor in a wide range of human inflammatory and infectious diseases.
14680507 Electrophoretic characterization of species of fibronectin bearing sequences from the N-te 2003 Fragments of fibronectin (FN) corresponding to the N-terminal heparin-binding domain have been observed to promote catabolic chondrocytic gene expression and chondrolysis. We therefore characterized FN species that include sequences from this domain in samples of arthritic synovial fluid using one-and two-dimensional (1D and 2D) Western blot analysis. We detected similar assortments of species, ranging from ~47 to greater than 200 kDa, in samples obtained from patients with osteoarthritis (n = 9) versus rheumatoid arthritis (n = 10). One of the predominant forms, with an apparent molecular weight of ~170 kDa, typically resolved in 2D electrophoresis into a cluster of subspecies. These exhibited reduced binding to gelatin in comparison with a more prevalent species of ~200+ kDa and were also recognized by a monoclonal antibody to the central cell-binding domain (CBD). When considered together with our previous analyses of synovial fluid FN species containing the alternatively spliced EIIIA segment, these observations indicate that the ~170-kDa species includes sequences from four FN domains that have previously, in isolation, been observed to promote catabolic responses by chondrocytes in vitro: the N-terminal heparin-binding domain, the gelatin-binding domain, the central CBD, and the EIIIA segment. The ~170-kDa N-terminal species of FN may therefore be both a participant in joint destructive processes and a biomarker with which to gauge activity of the arthritic process.
14994385 Erythromycin suppresses the expression of cyclooxygenase-2 in rheumatoid synovial cells. 2004 Mar OBJECTIVE: To investigate whether erythromycin (EM) can suppress the expression of cyclooxygenase-2 (COX-2) in rheumatoid synovial cells, and determine the mechanisms involved. Methods. Synovial tissues were obtained from 25 patients with rheumatoid arthritis (RA). Rheumatoid synovial cells were cultured with or without EM (0.1-1000 nM) in the presence of interleukin 1beta (IL-1beta) for various times. Protein expression of COX-2, and phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) were detected by Western blot. COX-2 messenger RNA (mRNA) was detected by RT-PCR. DNA binding activity of nuclear factor kappa B (NF-kB) was detected by ELISA. Results. IL-1beta-stimulated synovial cells expressed COX-2 protein. EM suppressed the IL-1beta-induced COX-2 protein expression in a dose-dependent manner and inhibited IL-1beta-induced p38 MAPK phosphorylation, which was correlated with COX-2 expression in synovial cells. In contrast, EM had no effect on DNA binding activity of NF-kB and ERK1/2 expression. CONCLUSION: Our results indicated that EM downregulated COX-2 expression by inhibiting the p38 MAPK cascade, but had no effect on NF-kB or ERK1/2, in rheumatoid synovial cells.
12096225 A 588-gene microarray analysis of the peripheral blood mononuclear cells of spondyloarthro 2002 Jul OBJECTIVES: To identify genes which are more highly expressed in the peripheral blood mononuclear cells (PBMC) of patients with spondyloarthropathy (SpA), rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in comparison to normal subjects. METHODS: A 588-gene microarray was used as a screening tool to select a panel of such genes from PBMC of these subjects and of normal subjects. Results were then validated by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The following genes were more highly expressed in arthritis patients than in normal subjects: macrophage differentiation marker MNDA (myeloid nuclear differentiation antigen), MRP8 and MRP14 (migratory inhibitory factor-related proteins); signalling molecules JAK3 (janus kinase 3) and MAP kinase p38 (mitogen-activated protein kinase); receptors TNFR2/p75, C-C-chemokine receptor type 1 (CCR1), C-X-C-chemokine receptor type 4 (CXCR4) and integrin beta1; and the cytokines/chemokines interleukin (IL) 1beta and IL-8. Expression of CXCR4 was unexpectedly high among all arthritis subjects. Using RT-PCR, ELISA and immunohistology, expression of stromal cell-derived factor 1 (SDF-1) was demonstrated in arthritis joints. CONCLUSIONS: The CXCR4/SDF-1 is a potential pro-inflammatory axis for RA, PsA and SpA.
11779766 Serum nitrate and nitrite levels in patients with rheumatoid arthritis, ankylosing spondyl 2002 Jan OBJECTIVE: To assess and compare serum nitrate and nitrite levels in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), and osteoarthritis (OA). METHODS: Thirty five patients with RA, 32 patients with AS, and 36 patients with OA were entered into this study. In addition, 30 healthy volunteers acted as a control group. Concentrations of nitrate and nitrite in serum were determined by direct and indirect Griess reactions. C reactive protein and erythrocyte sedimentation rate levels were determined as markers of systemic activity of disease (SAD) in RA and AS groups. RESULTS: Serum nitrate and nitrite levels were found to be higher in patients with AS and RA than in the OA group (p<0.01). In addition, serum nitrate and nitrite levels were higher in all three groups than in the control group (p<0.01). Moreover, serum nitrate and nitrite levels were higher in patients who had SAD than in those who had not in the RA and AS groups (p<0.01 and p<0.05, respectively), and there was a correlation between serum nitrate and nitrite concentrations and SAD variables in patients with RA (Spearman's r(s)=0.414, p<0.05 and r(s)=0.408, p<0.05, respectively) and AS (r(s)=0.421, p<0.05 and r(s)=0.412, p<0.05, respectively). CONCLUSION: The findings suggest that nitrate and nitrite production is enhanced in patients with inflammatory arthritis compared with OA. In addition, serum nitrate and nitrite levels are enhanced in patients with RA, AS, and OA compared with healthy subjects. Furthermore, there is a correlation between the SAD variables and serum nitrate and nitrite levels in patients with RA and AS.
15517297 [Conceptual and methodological basics of cost assessments in rheumatology]. 2004 Oct Cost-of-illness studies in rheumatic conditions show an enormous variability in reported costs. Reasons are-among others-a lack of standardization with regards to relevant cost domains and the utilization of various insufficiently validated costing sources. A flow scheme is presented which may serve as a systematic basis for a valid costing analysis. The scheme includes: i) Selection of relevant cost domains. A comprehensive matrix of cost domains may be used as a framework. According to the specific aims of any costing study individual domains might be selected. ii) An adequate level of detail has to be determined taking into account factors such as the validity of the data collection and the feasibility. iii) Appropriate objective (i. e. usage of administrative data) or subjective (i. e. patient-derived) data sources have to be identified under consideration of respective strengths and weaknesses. While administrative sources provide a valid access to costing data accessibility and feasibility are important advantages of patient-derived costing procedures. iv) During data collection the potential bias due to protocol-driven costs and the differentiation of disease-related from other health care costs should be considered. v) The data analysis should support a transparent presentation of the costing data both in physical and monetary units. In summary, no 'gold standard' has been established for costing studies yet. However, valid costing approaches might follow the flow scheme presented in this analysis.
15468353 Infusion-related reactions to infliximab in patients with rheumatoid arthritis in a clinic 2004 Oct OBJECTIVE: We describe infusion-related reactions to infliximab (during infusion or within 1 hour postinfusion) in patients with active rheumatoid arthritis (RA) treated in a quaternary care center. METHODS: We followed 113 patients for a mean of 60.6 +/- 28.9 weeks, obtaining 10.5 +/- 4.9 infusions per patient. RESULTS: We observed 1183 infusions resulting in 104 infusion reactions (8.8%). All reactions resolved within several hours following cessation of the infusion and none was serious enough to warrant hospitalization. Reactions included allergic reactions (pruritus, urticaria) in 4.2% of infusions, cardiopulmonary (hypotension, hypertension, tachycardia) in 3.0%, and miscellaneous reactions (headache, nausea, vomiting) in 2.0%. Reactions occurred in 8.0% of 3 mg/kg infusions and in 10.3% of 5 mg/kg infusions. Reactions occurred in 13.2% of infusions that involved antihistamine pretreatment compared to only 7.5% of infusions that involved no pretreatment. At both infliximab doses, there was a similar frequency of infusion reactions in patients pretreated due to a previous infusion (12.6%) compared to those pretreated strictly based on infusion number (14.7%). A number of the reactions involving antihistamine pretreatment may be explained by known side effects of diphenhydramine, including headache, dizziness, nausea, and palpitations. CONCLUSION: Infusion-related reactions to infliximab were infrequent, rarely severe, and easily manageable. The frequency of reactions was equivalent in patients treated with 3 mg/kg compared to 5 mg/kg. Reactions were significantly more frequent in infusions where patients were pretreated with the antihistamine diphenhydramine, compared to those not involving pretreatment.
11792880 Scintigraphy using a technetium 99m-labelled anti-E-selectin Fab fragment in rheumatoid ar 2002 Jan OBJECTIVE: We previously described a novel radiolabelled monoclonal antibody (1.2B6), which reacts with porcine E-selectin, for targeting activated endothelium as a means of imaging inflammatory disorders, and presented initial clinical work based on (111)In-labelled antibody. The aim of the present study was to evaluate a Fab fragment of 1.2B6 labelled with (99m)Tc in patients with rheumatoid arthritis (RA) by comparison with (i) (111)In-labelled 1.2B6 F(ab')(2) and (ii) conventional bone scanning. METHODS: (99m)Tc-1.2B6-Fab ( approximately 440 MBq) and (111)In-1.2B6-F(ab')(2) ( approximately 27 MBq) were compared in 10 patients using a double-isotope protocol. Images were obtained 4 and 20-24 h after injection. Two normal volunteers were also imaged. In a separate group of 16 patients, (99m)Tc-1.2B6-Fab and (99m)Tc-oxidronate ((99m)Tc-HDP) ( approximately 740 MBq) were compared on the basis of visual and semi-quantitative analysis of joint uptake (joint/soft tissue ratios) 4 h after injection. The respective biodistributions and blood clearances of the two 1.2B6 fragments were also compared. RESULTS: Image contrast was slightly better with (99m)Tc-Fab at 4 h but equal for the two tracers at 24 h. Diagnostic accuracy, taking joint tenderness or swelling as the clinical endpoint, was 76% for both fragments at 24 h. Plasma clearance of (99m)Tc-Fab was faster than that of (111)In-F(ab')(2) (t(1/2) 142 vs 421 min; P<0.0001). (99m)Tc-Fab appeared somewhat unstable in vivo, as shown by activity in the thyroid gland and bowel. The diagnostic accuracy of (99m)Tc-Fab was 88%, higher than that of (99m)Tc-HDP (57%) as a result of the low specificity of the latter in RA. Receiver operating characteristic (ROC) curve analysis using joint/soft tissue ratios as a variable cut-off showed that (99m)Tc-Fab discriminates better than (99m)Tc-HDP between actively inflamed and silent joints (Z=4.72; P<0.0001). No uptake of (99m)Tc-Fab was observed by inactive or normal joints, whereas (99m)Tc-HDP was taken up by all joints to a variable degree, making the decision as to whether a particular joint is actively involved or chronically damaged very difficult. CONCLUSION: (99m)Tc-anti-E-selectin-Fab scintigraphy can be used successfully to image synovitis with better specificity than (99m)Tc-HDP bone scanning. The advantages over (111)In-1.2B6-F(ab')(2) are easier availability of the radionuclide, improved physical properties and optimal imaging 4 h after injection.
11991745 Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory 2002 May Rheumatoid arthritis is a prevalent example of an inflammatory angiogenic disease, which is mediated by pro-inflammatory and pro-angiogenic cytokines such as tumor necrosis factor (TNF). To evaluate the effect of the potent anti-angiogenic factor endostatin on TNF-induced inflammatory arthritis, we injected an endostatin-expressing lentiviral vector directly into the joints of human TNF-transgenic mice before the onset of disease. Histological analysis of the injected joints 8 weeks later revealed that endostatin reduced blood vessel density within the synovial tissues and an overall mean arthritis index. In vitro and in vivo examination of the potential mechanism by which endostatin inhibited the arthritis revealed that endostatin blocks TNF-induced activation of JNK and JNK-dependent pro-angiogenic gene expression. These data suggest a novel mechanism by which endostatin inhibits angiogenesis, and demonstrates the potential utility of anti-angiogenic gene therapy for treatment of inflammatory arthritis.
12585577 Patient demographics as a predictor of the ten-year survival rate in primary total knee re 2003 Jan s the surgical indications for total knee replacement (TKR) expand to include younger, heavier and more active patients, knowledge of the effect of these demographic variables on the outcome and survival of the implant is increasingly important. Between November 1986 and September 1990, 402 patients underwent 562 primary cemented cruciate-retaining TKRs carried out by a single surgical team. The overall results showed a survival of 96.8% at 14 years with 1.44% lost to follow-up. Evaluating the demographics of these patients showed that certain groups fared significantly less well. The best results were seen in non-obese women with osteoarthritis who were over 60 years of age in whom there was ten-year survival of 99.4%. The worst results were in obese men with osteoarthritis who were less than 60 years of age in whom there was a ten-year survival of 35.7%. Caution should be exercised when considering TKR on a patient with this combination of poor risk factors. By identifying demographic factors at the time of consultation the surgeon is better able to predict the survival of the TKR. This information is important when considering the best options for treatment of a patient and in providing accurate information during preoperative counselling.
15196219 Increased activation-induced cell death in peripheral lymphocytes of rheumatoid arthritis 2004 Jul Recently, we have described a soluble survival signal for activated lymphocytes from CD14(+) cells. As a result of the importance of T lymphocytes in the pathogenesis of rheumatoid arthritis (RA), we speculate a possible role for CD14(+) cells in supporting the outgrowth of autoreactive lymphocytes in RA. To address this issue further, supernatants from activated CD14(+) cells (CD14 cocktails) in both normal controls and RA patients were collected. The relative strength of the CD14 cocktails from normal controls and RA patients was compared. The data showed that depletion of CD14(+) cells resulted in a much higher increase of activation-induced cell death (AICD) and a decrease of lymphocyte proliferation in the peripheral blood mononuclear cells of RA patients compared to normal controls. Interestingly, CD14 cocktails from RA patients provide much stronger protection against AICD compared to those from normal controls. The observed soluble survival signal from CD14(+) cells is a general phenomenon because CD14 cocktails prevent both phytohaemagglutinin A-p- and anti-CD3-induced AICD. Furthermore, supernatants collected from human dendritic cell cultures also prevent activated lymphocytes from undergoing AICD. The data implicate an important role of the CD14(+) cell and its secreted form of survival signal in the pathogenesis of RA.
12794819 Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor pr 2003 Jun OBJECTIVE: To investigate whether interleukin-6 (IL-6) is a regulator of vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA). METHODS: Serum VEGF levels in RA patients were assayed before and after 8 weeks or 24 weeks of maintenance therapy with humanized anti-IL-6 receptor monoclonal antibody (anti-IL-6R mAb). VEGF secreted by RA synovial fibroblasts cultured in the presence of IL-6, IL-1beta, and/or tumor necrosis factor alpha (TNFalpha) was measured. The inhibitory effect of anti-IL-6R mAb, recombinant IL-1 receptor antagonist (IL-1Ra), and anti-TNFalpha mAb on VEGF production was also examined. RESULTS: Serum VEGF levels in RA patients before anti-IL-6R mAb therapy were significantly higher than those in healthy controls (P < 0.0005). Treatment of RA patients with anti-IL-6R mAb normalized serum VEGF levels. In the in vitro study, IL-6 and IL-1beta each induced a slight amount of VEGF production in synovial cells, but TNFalpha did not. Although VEGF-inducing activity of these cytokines was not remarkable when they were added alone, IL-6 acted synergistically with IL-1beta or TNFalpha to induce VEGF production. There was no synergistic effect between IL-1beta and TNFalpha. In the presence of all of these cytokines, anti-IL-6R mAb eliminated the synergistic effect of IL-6, IL-1beta, and TNFalpha, while IL-1Ra or anti-TNFalpha mAb did not. CONCLUSION: Anti-IL-6R mAb therapy reduced VEGF production in RA. IL-6 is the pivotal cytokine that induces VEGF production in synergy with IL-1beta or TNFalpha, and this may be the mechanism by which IL-6 blockade effectively suppresses VEGF production in synovial fibroblasts.
14750259 [Cytokines and bone turnover markers]. 2002 OBJECTIVE: Bone turnover markers (osteocalcin, bone-ALP, beta-crosslaps--CTX) and cytokines (IL-1 alpha, IL-8 and IL-10) in hip joint fluid were analyzed in patients with aseptic loosening of prosthesis before revision surgery, in patients with rheumatoid arthritis and with idiopathic coxarthrosis for comparison. METHODS: Bone turnover markers were determined by electrochemiluminescence, colorimetric or ELISA method and cytokines by ELISA in joint fluid collected at the beginning of the surgery. RESULTS: Patients with loose implants had lower concentration of the resorption marker than cases with rheumatoid arthritis and coxarthrosis (7771 +/- 3322 vs 25986 +/- 16059 p < 0.01 and 23047 +/- 32556 pmol/L, p < 0.003) and over tenfold lower concentration of osteocalcin, the bone formation marker (p < 0.04 i p < 0.01). Concentration of IL-8 was elevated and similar in patients with loosening and rheumatoid arthritis while in cases with osteoarthrosis the mean value was twice lower. The anti-inflammatory IL-10 was highly elevated only in cases with prosthesis loosening. Additionally, a negative correlation was observed between CTX and IL-10 was and positive between IL-10 and time to revision surgery. CONCLUSIONS: We conclude that increased local production of inflammatory cytokines leading to uncoupling of bone turnover is a part of the loosening process.
15266062 Different cytokine profiles in patients with chronic and acute reactive arthritis. 2004 Oct OBJECTIVE: Analysis of cytokine production in patients with acute and chronic reactive arthritis (AcReA/ChrReA) in order to search for new treatment possibilities. METHODS: Cytokine production by peripheral blood and synovial fluid mononuclear cells (PBMCs/SFMCs) of 28 patients with AcReA, 27 patients with ChrReA, 26 patients with rheumatoid arthritis (RA) and 31 healthy controls was analysed by enzyme-linked immunosorbent assay (ELISA) and flow-cytometry. Production of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin (IL)-10 was measured by ELISA, while the percentages of TNF-alpha-, IFN-gamma- and IL-4-positive CD3+ cells were determined in the same groups of patients and healthy subjects using flow cytometry. RESULTS: Spontaneous TNF-alpha production observed in PBMCs of ChrReA, but not of AcReA, patients was significantly higher (P<0.001) than in healthy controls. The percentages of TNF-alpha-positive CD3+ blood cells in ChrReA exceeded that of RA patients and healthy controls (P<0.05 and P<0.001, respectively). Also, the percentages of IFN-gamma-positive CD3+ cells were significantly higher in peripheral blood and synovial fluid of ChrReA patients (P<0.05 and P<0.05, respectively) as compared with AcReA. In ChrReA spontaneous IL-10 production in PBMCs was similar to that observed in healthy controls, while in RA and AcReA the production of IL-10 was significantly increased (P<0.05 and P<0.05, respectively). IL-4 production was low in all study groups with no significant differences detected. CONCLUSIONS: High production of TNF-alpha and IFN-gamma detected in ChrReA supports the possible use of anti-TNF-alpha treatment in ChrReA.