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ID PMID Title PublicationDate abstract
9801782 Minimise outcome measures after knee replacement. 1998 In a previous study the "performance variability" of 15 different assessment systems after knee replacement was analysed. The notion that different knee evaluation systems measure different underlying factors was suggested. Three systems that seemed to have different underlying factors were selected, and a factor analysis was carried out to reduce the number of items in each group. The number of items could be reduced by 70%-82% with a minor loss of discriminating capacity. All instruments could be separated into items of pain, strength, mobility or stability. Pain measured on a visual analogue scale and self-selected walking speed were recommended for longitudinal monitoring of the treatment effect after knee replacement.
10783841 Is there a relationship between rheumatoid arthritis and periodontal disease? 2000 Apr AIM: The aim of this study was to determine whether there is a relationship between disease experience of rheumatoid arthritis and periodontal disease. METHODS: 1,412 individuals attending the University of Queensland's School of Dentistry were assessed for the prevalence of periodontal disease and rheumatoid arthritis. Analysis of data obtained from a self-reported health questionnaire and dental records was carried out and included: number of individuals referred for advanced periodontal care (test group); number of individuals attending for routine dentistry; determination of rheumatoid arthritis, cardiovascular disease and diabetes mellitus through self-reporting and assessment of prescription medications; assessment of periodontal disease through assessment of existing oral radiographs. RESULTS: In patients referred for periodontal treatment, the prevalence of self-reported rheumatoid arthritis was 3.95% which is significantly higher than that seen in patients not referred for periodontal treatment (0.66%) and also that reported in the general population (1%). Of those referred patients with rheumatoid arthritis, 62.5% had advanced forms of periodontal disease. These results were mirrored in the results of the self-reported prevalence of cardiovascular disease and diabetes mellitus which was consistent with the published higher prevalence in periodontal patients. CONCLUSIONS: Based on data derived from self-reported health conditions, and not withstanding the limitations of such a study, we conclude that there is good evidence to suggest that individuals with moderate to severe periodontal disease are at higher risk of suffering from rheumatoid arthritis and vice versa.
10422544 Update on clinical developments with celecoxib, a new specific COX-2 inhibitor: what can w 1999 Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for the relief of pain and inflammation, yet their use is tempered by the development of side effects, primarily in the gastrointestinal (GI) tract. It is now known that inhibition of the enzyme cyclooxygenase (COX) is the principal mechanism for both the efficacy and the toxicity of NSAIDs. Recent research has shown that COX exists as at least two isoenzymes, COX-1 and COX-2. Compelling evidence suggests that COX-1 synthesizes prostaglandins that are involved in the regulation of normal cell activity (including GI cytoprotection), whereas COX-2 appears to produce prostaglandins mainly at sites of inflammation. These findings led to the search for compounds that would inhibit COX-2 without affecting COX-1. Several agents are under investigation in this new therapeutic category, including celecoxib (SC-58635). Celecoxib was developed as an anti-inflammatory and analgesic agent, and has been studied in preclinical studies and in clinical trials. This paper focuses on the results of five key clinical trials of celecoxib: an efficacy trial in dental pain, a 2-week osteoarthritis (OA) efficacy trial, a 4-week rheumatoid arthritis (RA) efficacy trial, a 1-week endoscopic study of GI mucosal effects, and a 10-day study of effects on platelet function. The arthritis trials identified celecoxib doses that were effective in treating OA and RA and that were distinguished from placebo on standard arthritis scales. In the upper GI endoscopy study, no ulcers occurred in subjects receiving celecoxib or placebo, whereas 19% of subjects receiving naproxen developed gastric ulcers. In the platelet effects trial, no statistically significant difference from placebo was seen in the effect of celecoxib on platelet aggregation or bleeding time. In contrast, naproxen caused statistically significant reductions in platelet aggregation and a statistically significant increase in bleeding time. These preliminary trials show that celecoxib achieves analgesic and anti-inflammatory efficacy in arthritis through specific COX-2 inhibition without showing evidence of two of the toxic effects of COX-1 inhibition associated with NSAIDs.
11263764 A randomized two-year study of the effects of dynamic strength training on muscle strength 2001 Mar OBJECTIVE: To evaluate the impact of a 2-year program of strength training on muscle strength, bone mineral density (BMD), physical function, joint damage, and disease activity in patients with recent-onset (<2 years) rheumatoid arthritis (RA). METHODS: In this prospective trial, 70 RA patients were randomly assigned to perform either strength training (all major muscle groups of the lower and upper extremities and trunk, with loads of 50-70% of repetition maximum) or range of motion exercises (without resistance) twice a week; all were encouraged to engage in recreational activities 2-3 times a week. All patients completed training diaries (evaluated bi-monthly) and were examined at 6-month intervals. All were treated with medications to achieve disease remission. Maximum strength of the knee extensors, trunk flexors and extensors, and grip strength was measured with dynamometers. BMD was measured at the femoral neck and lumbar spine by dual x-ray densitometry. Disease activity was determined by the Disease Activity Score, the extent of joint damage by the Larsen score, and functional capacity by the Health Assessment Questionnaire (HAQ); walking speed was also measured. RESULTS: Sixty-two patients (31 per group) completed the study. Strength training compliance averaged 1.4-1.5 times/week. The maximum strength of all muscle groups examined increased significantly (19-59%) in the strength-training group, with statistically significant improvements in clinical disease activity parameters, HAQ scores, and walking speed. While muscle strength, disease activity parameters, and physical function also improved significantly in the control group, the changes were not as great as those in the strength-training group. BMD in the femoral neck and spine increased by a mean +/- SD of 0.51 +/- 1.64% and by 1.17 +/- 5.34%, respectively, in the strength-training group, but decreased by 0.70 +/- 2.25% and 0.91 +/- 4.07% in the controls. Femoral neck BMD in the 17 patients with high initial disease activity (and subsequent use of oral glucocorticoids) remained constantly at a statistically significantly lower level than that in the other 45 patients. CONCLUSION: Regular dynamic strength training combined with endurance-type physical activities improves muscle strength and physical function, but not BMD, in patients with early RA, without detrimental effects on disease activity.
14635272 Ambulatory care or home-based treatment? An economic evaluation of two physiotherapy deliv 2000 Aug OBJECTIVE: To assess the difference in costs of home-based versus clinic-based physiotherapy (PT) for patients with rheumatoid arthritis (RA) from a societal perspective. METHODS: A cost analysis was performed using statistical and financial information provided by The Arthritis Society, Ontario Division, from April 1, 1997 to March 30, 1998. Cost estimates included treatment costs and costs borne by patients. A sensitivity analysis was conducted to examine the effect of altering the valuation of treatment time and patient employment status. RESULTS: Total costs per case were $210.87 for the home setting, and $183.87 for the clinic setting when patients were employed. Sensitivity analysis did not change the trend of the results. The estimated start-up costs for an arthritis clinic were between $302.90 and $652.40. From the perspective of the health care system, these costs would be recovered after serving 4 to 8 RA patients at a clinic. CONCLUSION: The findings suggest that ambulatory PT care is less costly than home-based services for people with RA based on The Arthritis Society model. Further studies should be conducted to examine the effectiveness and the possible adverse consequences of alternative settings for service delivery.
9548992 Mast cells in osteoarthritic and rheumatoid arthritic synovial tissues of the human knee. 1998 Feb The distribution and density of mast cells in the normal and diseased synovial membranes were investigated. The mast cell count (MCC) in the osteoarthritic (OA) synovium (36.9 +/- 26.9 cells/mm2) was significantly higher than that in the rheumatoid arthritic (RA) synovium (18 +/- 12.3 cells/mm2). There was a marked positive correlation between the MCC and the volume of joint fluid in OA (r = 0.544). There was a marked negative correlation between the MCC and the volume of joint fluid in RA (r = -0.478). The synovial inflammatory score had a poor correlation with the MCC in OA (r = 0.377) and RA (r = 0.305). No correlation was noted between MCC and age, sex, roentgenographic grades, disease duration, C-reactive protein or leucocyte number in synovial fluid. Our data suggests, thus, that mast cells could be involved in the pathogenesis of inflammatory diseases of the synovium, especially in the mechanism of hydroarthrosis.
9817125 Performance of the Norwegian SF-36 Health Survey in patients with rheumatoid arthritis. II 1998 Nov The performance of the SF-36 was compared with disease-specific health status instruments (Arthritis Impact Measurements Scales [AIMS2], Modified Health Assessment Questionnaire [MHAQ] and visual analogue scales) in 1030 patients with rheumatoid arthritis (mean age 62.3 years, 79% females, mean disease duration 12.9 years, 48% rheumatoid factor positive). The scales performed similarly in known group comparisons (age cohorts, disease severity, disease activity, comorbidity). The SF-36 physical functioning scale correlated -0.69 and -0.73 with the MHAQ and AIMS2 physical scales, respectively. A strong negative correlation was found with the walking and bending subscale of AIMS2 (r = -0.80), a substantial negative correlation with mobility (r = -0.65), and moderate correlations with the scales for hand/finger and arm function (r = -0.52 and r = -0.53). Frequency distributions of scores revealed more skewed distributions of the AIMS2 physical scale and the MHAQ scale than the physical functioning scale of the SF36, whereas the pain and mental health scales were distributed similarly. In conclusion, the SF-36 performs well in patients with rheumatoid arthritis. The physical functioning scale of the SF-36 does not seem to capture all aspects of physical health in rheumatoid arthritis patients, but may be more sensitive than disease-specific measures to low levels of physical disability.
10617995 n-3 fatty acid supplements in rheumatoid arthritis. 2000 Jan Ingestion of dietary supplements of n-3 fatty acids has been consistently shown to reduce both the number of tender joints on physical examination and the amount of morning stiffness in patients with rheumatoid arthritis. In these cases, supplements were consumed daily in addition to background medications and the clinical benefits of the n-3 fatty acids were not apparent until they were consumed for > or =12 wk. It appears that a minimum daily dose of 3 g eicosapentaenoic and docosahexaenoic acids is necessary to derive the expected benefits. These doses of n-3 fatty acids are associated with significant reductions in the release of leukotriene B(4) from stimulated neutrophils and of interleukin 1 from monocytes. Both of these mediators of inflammation are thought to contribute to the inflammatory events that occur in the rheumatoid arthritis disease process. Several investigators have reported that rheumatoid arthritis patients consuming n-3 dietary supplements were able to lower or discontinue their background doses of nonsteroidal antiinflammatory drugs or disease-modifying antirheumatic drugs. Because the methods used to determine whether patients taking n-3 supplements can discontinue taking these agents are variable, confirmatory and definitive studies are needed to settle this issue. n-3 Fatty acids have virtually no reported serious toxicity in the dose range used in rheumatoid arthritis and are generally very well tolerated.
9196876 Anti-CD4 monoclonal antibody (mAb) and anti-idiotypic mAb to anti-CD4 in the therapy of au 1997 Mar The present report critically reviews the rationale, experimental and clinical effectiveness and limits of anti-CD4 monoclonal antibody (mAb) therapy. References are also made to a novel approach involving active immunotherapy and an anti-idiotypic mAb bearing the internal image of human CD4 antigen. Preliminary observations concerning the effects of this treatment in one patient with rheumatoid arthritis and in one patient with systemic lupus erythematosus are reported.
11451106 Total condylar knee replacement: a 20-year followup study. 2001 Jul Between 1976 and 1979, 220 total knee replacements were done on 164 patients using the Total Condylar Knee replacement. The diagnosis was rheumatoid arthritis in 111 knees and osteoarthritis in 109 knees. Patients with 157 knees are known to have died as of December 1998, leaving 63 knees in patients who are still alive. Twelve patients with 18 knees were lost to followup. The average 20-year followup data (range, 18-22 years) are presented for 45 knees in 30 patients using Knee Society evaluations. The average Knee Society clinical score for the surviving patients was 88 points, and the average functional score was 58 points. The radiographic followup averaged 19 years. The average overall alignment was 3 degrees valgus. Femoral lucencies were present in 17 of 40 adequate lateral views, most commonly about the anterior and posterior surfaces. Two femoral components were loose. Twenty-two tibial components had radiolucencies; four radiolucencies were circumferential. The remaining 41 knees retained a well-fixed cemented central peg despite proximal interface lucencies. From the group of 220 knees, 14 revisions have been done at an average of 11.4 years postoperative. Two knee replacements were revised for isolated tibial loosening, whereas one knee replacement had isolated femoral loosening. Three knee replacements were revised for loosening of both components, and one was revised for isolated patellar loosening. Four patients had sepsis develop; three of these four patients were treated with two-stage revision, and one underwent fusion. Three patients were treated for supracondylar fractures. The Total Condylar Knee replacement maintains excellent durability at 20-years followup.
11593962 Arginase levels are increased in patients with rheumatoid arthritis. 2001 Jun Arginase and nitric oxide synthase (NOS) compete for the same substrate, L-arginine. The reciprocal regulation of arginase and NOS in L-arginine-metabolizing pathways has recently been demonstrated. Since NOS is involved in the inflammation of human arthritides, we hypothesized that this reciprocal regulation might also occur within the inflamed synovium. The present study shows that both serum arginase activity and protein levels were significantly higher in patients with rheumatoid arthritis (RA) than in patients with systemic lupus erythematosus (SLE) or osteoarthritis (OA) or in healthy controls. Arginase protein concentrations in supernatants of monocyte cultures from RA patients were also significantly higher than in those from SLE or OA patients or healthy controls. In RA patients, there was a significant correlation between the serum concentrations of arginase protein and rheumatoid factor (r = 0.82, p < 0.0001). These data indicate that increased arginase production is seen in RA patients, but not in other immune-related diseases, suggesting that increased arginase production is unique to, and may play an important role in, the pathogenesis of RA disease.
10329846 IL-6 synthesis by rheumatoid synoviocytes is autonomously upregulated at the transcription 1999 May BACKGROUND: Involvement of IL-6 in the pathogenesis of rheumatoid arthritis has recently been demonstrated, but the mechanism of its production by rheumatoid synoviocytes is still poorly defined. OBJECTIVE: The purpose of this study was to clarify the cellular and molecular mechanisms involved in the spontaneous production of IL-6 by fibroblast-like synoviocytes obtained from patients with rheumatoid arthritis. METHODS: Cloned synoviocytes were established by the limiting dilution method. IL-6 synthesis was evaluated by ELISA and Northern blot analysis. IL-6 gene transcription and transcription factors were analyzed by the transient transfection of luciferase reporter plasmids and the electrophoretic mobility shift assay, respectively. RESULTS: IL-6 synthesis by cloned rheumatoid synoviocytes was spontaneously upregulated at the transcriptional level. Enhanced IL-6 production by high-producing clones was independent of cytokines from other cell populations or autocrine production of tumor necrosis factor-alpha and IL-1. Deletion analysis showed that the IL-6 promoter was regulated by 2 positive elements (-159 to -142 base pair and -77 to -59 base pair). The transcriptional activity of the latter element was upregulated in clones showing high IL-6 production. The binding activity of NF-kappaB p50/p65 heterodimer and RBP-Jkappa was enhanced in these clones. CONCLUSION: IL-6 production by rheumatoid synoviocytes is autonomously upregulated at the transcriptional level and spontaneous activation of NF-kappaB and RBP-Jkappa seems to be involved.
10331119 Radiographic manifestations of rheumatic diseases affecting the foot and ankle. 1999 Apr Radiologic evaluation of the foot and ankle affected by rheumatic disease involves objective assessment of the radiologic changes that may be associated with a specific arthritis. Assessment of the severity of involvement and evaluation of progression or regression of the disease are important in the treatment regimen and ultimate clinical outcome of every patient.
10679307 Induction of COX-2 expression by nitric oxide in rheumatoid synovial cells. 2000 Feb 24 Prostaglandins formed by cyclooxygenase (COX) enzymes are important mediators of inflammation. The contribution of inducible COX-2 in the rheumatoid synovium is well documented. In this study, we evaluated the contribution of nitric oxide (NO) to COX-2 expression in rheumatoid synovial cells. Exposure of rheumatoid synovial cells to a NO donor, SNAP, induced COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated that COX-2 mRNA was induced in SNAP-treated synovial cells. Dexamethasone at therapeutic concentrations markedly inhibited this NO-mediated COX-2 expression in synovial cells. In contrast to its effect on COX-2 expression, SNAP did not affect the constitutive expression of COX-1 in rheumatoid synovial cells. Our findings suggest that NO is an important modulator of COX-2 expression and that glucocorticoids exert their anti-inflammatory action in rheumatoid synovium, at least in part, by suppression of COX-2 induction.
9583065 Pregnancy immunology and autoimmune disease. 1998 Apr The advent of molecular biologic techniques has resulted in the recognition of bidirectional traffic of cells at the maternal-fetal interface. In this light, and because women are preferentially affected by a wide variety of autoimmune diseases, the subject of pregnancy immunology is of special interest. That pregnancy often induces remission of rheumatoid arthritis is an intriguing biologic observation for which further understanding may yield insights into disease pathogenesis. Another important question is the effect of pregnancy on susceptibility to autoimmune diseases. This question is highlighted by the recent finding that chimeric cells can persist for many years after pregnancy completion. At present, the biologic significance of microchimerism from pregnancy is an area of research that is for the most part unexplored.
11603672 What went wrong in triple arthrodesis? An analysis of failures in 21 patients. 2001 Oct Three hundred seven triple arthrodeses were done on 282 patients with rheumatic diseases between 1995 and 1999. Solid and painless fusion was achieved in 261 patients (93%, 286 arthrodeses). Twenty-one arthrodeses (in 21 patients) that failed were analyzed. Fourteen (66%) malunions, six (29%) nonunions, and one (5%) painful foot without malunion or nonunion were found. Of the failed procedures, valgus alignment was present in 13 feet and varus alignment was present in eight feet. The most common cause of failure was a misjudgment in the surgical technique, which occurred in 12 of 21 (57%) patients based on inadequate correction and repositioning of hindfoot deformity. In four (19%) patients, additional ankle destruction and instability was overlooked as a cause of malalignment. Revision triple arthrodesis was successful in 18 of 21 (86%) patients. Triple fusion offers challenges in surgical technique, postoperative treatment, and rehabilitation. Understanding the complexity of the rheumatic hindfoot is important when performing triple arthrodesis in patients with severe deformities manifesting typically as calcaneovalgus and pes planus.
11759236 [Chrysiasis]. 2001 Oct We describe the case of a 78-year old woman, with rheumatoid arthritis, 3 years of regular parenteral gold administration and Chrysiasis. Chrysiasis is a rare permanent pigmentation of the skin resulting from the parenteral administration of gold. The cause of the pigmentation is multifactorial and not fully established at the moment.
11409152 Disease modifying antirheumatic drugs: longterm safety issues. 2001 Jun The trend for more aggressive management of rheumatoid arthritis includes earlier introduction of disease modifying antirheumatic drugs (DMARD). As patients may continue their therapy for several decades instead of several years, the evaluation of benefit versus risk of DMARD with particular emphasis on longterm safety is essential. Longterm safety assessment is difficult for a number of reasons: there are relatively few trials that have followed patients beyond 5 years and the use of a combination of DMARD therapy with nonsteroidal antiinflammatory drugs and corticosteroids complicates the assessment of an observed adverse event with a particular drug. This review of longterm studies incorporating DMARD provides insight into adverse events associated with currently available DMARD.
11219391 Mast cell activation and its relation to proinflammatory cytokine production in the rheuma 2000 INTRODUCTION: Increased numbers of mast cells (MCs) are found in the synovial tissues and fluids of patients with rheumatoid arthritis (RA), and at sites of cartilage erosion. MC activation has been reported for a significant proportion of rheumatoid specimens. Because the MC contains potent mediators, including histamine, heparin, proteinases, leukotrienes and multifunctional cytokines, its potential contributions to the processes of inflammation and matrix degradation have recently become evident. Proinflammatory cytokines are important mediators of inflammation, immunity, proteolysis, cell recruitment and proliferation. Tumour necrosis factor (TNF) reportedly plays a pivotal role in the pathogenesis o RA, especially its ability to regulate interleukin (IL)-1beta expression, this being important for the induction of prostanoid and matrix metalloproteinase production by synovial fibroblasts and chondrocytes. IL-15 has been assigned numerous biological effects and has been assigned numerous biological effects and has been implicated as an important factor in TNF-alpha expression by monocyte/macrophages. Some in vitro studies have placed IL-15 upstream from TNF-alpha in the cytokine cascade, suggesting an interdependence between TNF, IL-1 and IL-15 for the promotion of proinflammatory cytokine expression in the rheumatoid joint. AIMS: To examine the in situ relationships of TNF-alpha, IL-1beta and IL-15 in relation to MC activation in rheumatoid tissues by use of immunolocalization techniques; and to compare quantitatively the proinflammatory cytokine production by specific cell cultures and rheumatoid synovial explants with and without exposure to a MC secretagogue. MATERIALS AND METHODS: Samples of rheumatoid synovial tissue and cartilage-pannus junction were obtained from patients (n=15) with classic late-stage RA. Tissue sections were immunostained for MC (tryptase) and the proinflammatory cytokines IL-1, TNF-alpha and IL-15. Rheumatoid synovial tissue explants were cultured in Dulbecco's modified Eagles medium (DMEM) containing either the MC secretagogue rabbit antihuman immunoglobulin (Ig)E, or control rabbit IgG. Primary rheumatoid synovial cell cultures, human articular chondrocytes, synovial fibroblasts and synovial macrophages were prepared as described in the full article. Conditioned culture media from these cultures were collected and assayed for IL-1beta, TNF-alpha and IL-15 using enzyme-linked immunosorbent assay methodology. RESULTS: Immunohistological studies of rheumatoid synovial tissues have demonstrated local concentrations of MCs in most specimens of the rheumatoid lesion. Sites of MC activation were associated with localized oedema, and TNF-alpha, IL-1alpha and IL-1beta production by a proportion of mononuclear inflammatory cells. By contrast, no evidence was found for IL-15 production in tissue sites containing either intact or activated MCs, and IL-15 expression, when observed, bore no relation to tissue sites where TNF-alpha and IL-1beta were evident. The immunodetection of IL-15 was restricted to microfocal sites and was not typical of most junctional specimens, but was associated with a proportion of articular chondrocytes in a minority of junctional specimens. MC activation within synovial explant cultures was induced by the addition of polyclonal antibody to human IgE. MC activation significantly reduced the levels of TNF-alpha and IL-1beta released into the medium, this representing approximately 33% of control values. By contrast, MC activation had little effect of the levels of IL-15 released into the culture medium, the average value being very low in relation to the release of TNF-alpha and IL-1beta. Thus, induced MC activation brings about changes in the amounts of released tryptase, TNF-alpha and IL-1beta, but not of IL-15. Four preparations of primary rheumatoid synovial cell cultures produced more IL-1beta than TNF-alpha, with only modest values for IL-15 production, indicating that all three cytokines are produced and released as free ligands by these cultures. Of specific cell types that produced IL-15 in vitro, macrophages produced more than fibroblasts, which in turn produced more than chondrocytes. This demonstrates that all three cell types have the potential to produce IL-15 in situ. DISCUSSION: The biological consequences of MC activation in vivo are extremely complex, and in all probability relate to the release of various combinations of soluble and granular factors, as well as to the expression of appropriate receptors by neighbouring cells. The subsequent synthesis and release of cytokines such as TNF-alpha and IL-1 may well follow at specific stages after activation, or may be an induced cytokine response by adjacent macrophagic or fibroblastic cells. However, because no IL-15 was detectable either in or around activated or intact MCs, and the induced MC activation explant study showed no change in IL-15 production, it seems unlikely that the expression of this cytokine is regulated by MCs. The immunohistochemistry (IHC) demonstration of IL-15 at sites of cartilage erosion, and especially by some chondrocytes of articular cartilage, showed no spatial relationship with either T cells or neutrophils, and suggests other functional properties in these locations. The lack of evidence for an in situ association of IL-15 with TNF and IL-1 does not support a role for IL-15 in a proinflammatory cytokine 'cascade', as proposed by other in vitro experiments. We believe that sufficient evidence is available, however, to suggest that MC activation makes a significant contribution to the pathophysiological processes of the rheumatoid lesion.
9058649 Rheumatoid synovial fibroblasts are stimulated by the cellular adhesion to T cells through 1997 Mar OBJECTIVE: To determine if T cells stimulate synovial fibroblasts to produce inflammatory cytokines through cellular adhesion in synovitis of rheumatoid arthritis (RA). METHODS: Immunohistochemical staining, flow microfluorometry, adhesion assay, ELISA, and Northern blot analysis to determine production of interleukin-1beta (IL-1beta) from RA synovium and RA synovial fibroblast-like cell line. RESULTS: We observed the following novel features of cellular adhesion of T cells to synovial fibroblasts, which suggest a role for induction of cytokine production in synovial fibroblasts: (a) CD11a (lymphocyte function associated antigen-1 alpha) positive T cells accumulated around CD54 [intercellular adhesion molecule (ICAM-1)] positive synoviocytes in active RA synovium, shown by immunohistochemical studies: (b) synovial fibroblastic cell line E11 expressed a single adhesion molecule ICAM-1, the expression of which was not affected by IL-1beta; (c) E11 adhered to phorbol myristate acetate (PMA) activated T cells within 30 min, not resting T cells, and its adhesion was completely inhibited by anti-LFA-1 monoclonal antibody (Mab); (d) pretreatment of E11 with IL-1beta did not affect the adhesion of E11 to PMA activated T cells; (e) IL-1beta production and IL-1beta mRNA transcription from E11 were induced by the addition of T cells in a cell number dependent manner and the induced production and transcription were inhibited by anti-LFA-1 Mab. CONCLUSION: T cells infiltrating the synovium may play a pivotal role in the pathogenesis of RA, by inducing IL-1beta production of synovial fibroblasts by sequential events, namely, T cell-synoviocyte cellular adhesion through LFA-1/ICAM-1, signal transduction, and production of IL-1beta induced by the cellular adhesion.