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ID PMID Title PublicationDate abstract
20840673 Quantitative determination of the diagnostic accuracy of the synovitis score and its compo 2010 Sep AIMS: To assess the diagnostic accuracy of a three-component synovitis score and to determine the relative contribution of each of its components to its overall discriminatory power. METHODS AND RESULTS: The synovitis score was determined in 666 synovial specimens: normal synovium, n = 33; post-traumatic arthropathy (PtA), n = 29; osteoarthritis (OA), n = 221; psoriatic arthritis (PsA), n = 42; and rheumatoid arthritis (RA), n = 341. The discriminatory abilities of the score and its components were quantified with binary and multicategory receiver operating characteristic (ROC) analysis. The score differentiated all arthropathies accurately from normal tissue (area under the ROC curve, AUC: 0.87-0.98) and RA from OA or PtA (AUC: 0.85 for both), but could not distinguish well within pairs of inflammatory or degenerative arthropathies. AUCs of the intimal hyperplasia and stromal cellularity components correlated with the AUCs of the complete score markedly more strongly (r = 0.94 and 0.91, respectively) than the inflammatory infiltration component (r = 0.60). Multicategory ROC analysis ranked the score several-fold higher than any of its components, and the components in the order stromal cellularity>intimal hyperplasia>infiltration. CONCLUSION: Combining three distinct histological parameters into a three-component score produces greatly increased overall diagnostic power. The discriminatory ability of the score stems more from measuring proliferative than infiltrative aspects of synovitis.
19282407 A midterm follow-up study of bioreconstructive polylactide scaffold implants in metacarpop 2009 Apr This paper presents the results of a prospective study of 80 metacarpophalangeal joint arthroplasties, in which biodegradable polylactide 96/4 copolymer scaffolds were used. Twenty-three rheumatoid arthritis patients were assessed at an average of 59 months after operation, which exceeds the resorption time of P(L/D)LA 96/4 according to animal experiments. Palmar subluxation exceeded half of the bone thickness in 39 joints before operation and in nine at the last follow-up. Ulnar deviation decreased from 25 degrees to 5 degrees , extension deficit from 32 degrees to 15 degrees and active flexion from 76 degrees to 63 degrees . The results are comparable with published data on silicone implant arthroplasties. Implant resorption did not induce any significant osteolysis in the medium term and the restoration of the structure and function of the hand was maintained after implant resorption, probably as the guided fibrous tissues had replaced the dissolved implant.
20836843 Development of a macromolecular prodrug for the treatment of inflammatory arthritis: mecha 2010 INTRODUCTION: The purpose of the present manuscript is to test the hypothesis that arthrotropic localization and synovial cell internalization account for the unique capacity of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex, a macromolecular prodrug of dexamethasone) to induce sustained amelioration of joint inflammation and inhibition of tissue damage in an animal model of inflammatory arthritis. METHODS: Rats with adjuvant-induced arthritis (AA) were treated with P-Dex, free dexamethasone, saline or HPMA homopolymer. To define the biodistribution of P-Dex, conjugates with different imaging labels were given to AA rats and analyzed. Isolated joint tissues were evaluated by fluorescence-activated cell sorting (FACS) and immunohistochemical staining. Cellular uptake of P-Dex and its effects on apoptosis and production of proinflammatory cytokines were examined using human monocyte-macrophages and fibroblasts. RESULTS: A single systemic administration of P-Dex completely suppressed AA for >20 days. Magnetic resonance imaging demonstrated higher HPMA copolymer influx into the inflamed joints than the normal joints. Immunohistochemistry and FACS analyses of arthritic joints revealed extensive uptake of the polymer conjugate by synovial fibroblasts and myeloid lineage cells. The capacity of P-Dex to suppress inflammation was confirmed in monocyte-macrophage cultures in which P-Dex treatment resulted in suppression of lipopolysaccharide-induced IL-6 and TNFα release. Similarly, TNFα-induced expression of matrix metalloproteinases (MMP1 and MMP3) in synovial fibroblasts from a rheumatoid arthritis patient was suppressed by P-Dex. P-Dex showed no detectable effect on monocyte apoptosis. CONCLUSIONS: P-Dex provides superior and sustained amelioration of AA compared with an equivalent dose of free dexamethasone. The arthrotropism and local retention of P-Dex is attributed to the enhanced vascular permeability in arthritic joints and the internalization of P-Dex by synovial cells. The uptake and processing of P-Dex by macrophages and fibroblasts, and downregulation of proinflammatory mediators, provides an explanation for the sustained anti-inflammatory efficacy of P-Dex in this model of inflammatory arthritis.
18339664 Cortical hand bone loss after 1 year in early rheumatoid arthritis predicts radiographic h 2009 Mar OBJECTIVE: To examine 1-year hand bone loss in early rheumatoid arthritis (RA) as a predictor of radiographic damage at 5-year and 10-year follow-up METHODS: A total of 136 patients with RA (disease duration 0-4 years) were followed for 10 years with clinical data and hand radiographs. Joint damage was scored according to the van der Heijde modification of the Sharp method (vdH Sharp score) and hand bone mineral density (BMD) was measured by digital x ray radiogrammetry (DXR). Group comparisons, correlation analyses and multivariate analyses were performed to evaluate the relationship between hand bone loss and radiographic joint damage. RESULTS: Patients with hand BMD loss at 1 year had a higher median increase in vdH Sharp score compared to patients without loss at 5 years (12 vs 2, p = 0.001) and 10 years (22 vs 4, p = 0.002). In a linear regression model adjusting for age, gender, baseline C-reactive protein (CRP), anti-cyclic citrullinated peptide (CCP), IgM rheumatoid factor (RF) and radiographic damage, absolute hand DXR-BMD loss at 1 year was an independent predictor of radiographic outcome at 5 years (p<0.01) and 10 years (p = 0.02). In a logistic regression model the odds ratio (95% CI) for radiographic progression among patients with hand BMD loss was 3.5 (1.4 to 8.8) and 3.5 (1.4 to 8.4) at 5 and 10 years, respectively. CONCLUSION: Early hand bone loss measured by DXR-BMD is an independent predictor of subsequent radiographic damage. Our findings support that quantitative hand bone loss in RA precedes radiographic joint damage and may be used as a tool for assessment of bone involvement in RA.
20456616 Sicca symptoms, and lacrimal and salivary flow in Albanian patients with rheumatoid arthri 2010 Sep BACKGROUND: Rheumatoid arthritis affects primarily the synovial joints, but is often accompanied by extra-articular manifestations, including lacrimal and salivary gland involvement. The aim of the present study was to estimate the prevalence of ocular and oral sicca symptoms and reduced lacrimal and salivary flow in rheumatoid arthritis and the relation between sicca symptoms and objective measures of lacrimal and salivary flow. METHODS: We examined 88 consecutive hospitalized patients with rheumatoid arthritis and 88 age- and gender-matched healthy controls. The examination included the standardized questionnaire for keratoconjunctivitis sicca and xerostomia which forms part of the European criteria for Sjögren's syndrome, the Schirmer's I test and measurement of unstimulated whole salivary flow rate. RESULTS: A significantly higher proportion of patients (40.9%) reported ocular sicca symptoms than healthy matched controls (8.0%). Further, a significantly higher proportion of patients (44.3%) reported oral sicca symptoms compared to controls (13.6%). 48.9% of the patients had low Schirmer I score, compared to 20.5% of controls. Reduced salivary flow was found in 27.3% of patients, compared to 9.1% of controls. The differences in lacrimal and salivary flow between patient and control group were statistically significant. The minimum prevalence of secondary Sjögren's syndrome was 14.8%. Weak association was observed between sicca symptoms and the objective measures of lacrimal and salivary flow in patients, and no association was detected in control subjects. CONCLUSIONS: Sicca symptoms and reduced lacrimal and salivary flow were common manifestations in rheumatoid arthritis and should be given adequate consideration during management of patients with rheumatoid arthritis.
20374312 Effect of conjugated linoleic acids, vitamin E and their combination on the clinical outco 2009 Apr BACKGROUND: Despite beneficial effects of conjugated linoleic acids (CLAs) in animal studies, there is little information on their effects on human inflammatory and autoimmune diseases. AIM: To investigate the effects of CLAs as an adjuvant therapy on the clinical manifestations of rheumatoid arthritis (RA) in adults with an active disease. METHODS: In a randomized, double-blind placebo-controlled trial, 87 patients with active RA were divided into four groups receiving one of the following daily supplements for 3 months: group C: CLAs 2.5 g equivalent to 2 g mixture of cis 9-trans 11 and trans 10-cis12 CLAs at a rate of 50/50; group E: vitamin E: 400 mg; group CE: CLAs and vitamin E at above doses; group P: placebo. Serum alpha-tocopherol was determined by high-performance liquid chromatography. Clinical data was determined by physician examination and filling the questionnaire by interview. Complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP) and rheumatoid factor (RF) were measured in each patient. DAS28 (diseases activity score) was also determined. RESULTS: A 3-month supplementation resulted significant reduction in DAS28, pain and morning stiffness in the groups C and CE compared with group P (P < 0.05). Compared with the baseline, ESR levels decreased significantly in the groups C (P < or = 0.05), E (P < or = 0.05) and CE (P < or = 0.001). Group CE had significantly lower ESR levels than group P (P v 0.05). CRP dropped non-significantly in all four groups (P > 0.1). The reduction of white blood cell count was significant in group CE compared with other groups (P < 0.05). Decrease in platelet count was non-significant in groups CE, C, and E. Changes in RF, body mass index, red blood cell count and hemoglobin were not significant in four groups, while RF decreased non-significantly in groups CE and E. In comparison with the baseline, alpha-tocopherol increased significantly in groups C (P < or = 0.05), E (P < or = 0.01) and CE (P < or = 0.001) and in groups E and CE compared with group P. CONCLUSION: CLA supplementation resulted in significant improvement in clinical manifestation among RA patients and may be useful in their treatments.
20471884 Isolated cerebral vasculitis associated with rheumatoid arthritis. 2010 Jul Central nervous system involvement in rheumatoid arthritis is infrequent. Inflammatory lesions described in the literature are limited to rheumatoid nodules and vasculitis. We report on a 71-year-old woman who presented with a 1-month history of headache and dysarthria, and who had suffered seropositive rheumatoid arthritis without extra-articular complications, for 15 years. Magnetic resonance imaging showed a high-intensity image in FLAIR-weighted sequences in the right cerebral hemisphere, with meningeal gadolinium enhancement. A brain biopsy revealed necrotizing and lymphocytic vasculitis in the meninges as well as cerebral parenchyma. The patient received treatment with high-dose intravenous methylprednisolone with radiological improvement at 6-month follow-up. She remained neurologically asymptomatic in subsequent years. Three years after the onset of neurological symptoms, she was admitted to the hospital with choluria and jaundice. On the fiftieth day of hospitalization, she died from bronchopneumonia. The autopsy showed no signs of vasculitis. Cerebral vasculitis is an infrequent complication in RA. High-doses of intravenous corticosteroids may be an effective treatment.
19222518 Effects of tumor necrosis factor-alpha blockade on metabolic syndrome components in psoria 2009 Jan Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic T cell-mediated inflammatory diseases that manifest not only in the skin and joints but also in the form of cardiometabolic disturbances, which include insulin resistance, dyslipidemia, and obesity. Thus, PsO and PsA patients are predisposed to metabolic syndrome (MetS), diabetes, and cardiovascular disease. In recent years, the introduction of targeted therapy in the form of tumor necrosis factor-alpha (TNF-alpha) antagonists, such as infliximab, etanercept, and adalimumab has been an important and effective addition to the treatment armamentarium for PsO and PsA. Although TNF-alpha antagonists have produced promising results clinically in reducing cutaneous and joint manifestations of PsO and PsA, their effects on MetS components in these patients are presently unclear. This review summarizes the current limited evidence on the effects of TNF-alpha antagonists on MetS components in PsO and PsA patients and extrapolates from related literature in rheumatoid arthritis, which is also a T cell-mediated inflammatory disease, for additional information.
19093117 An unusual central nervous system involvement in rheumatoid arthritis: combination of pach 2009 Sep Severe primary central nervous system (CNS) involvement such as vasculitis and pachymeningitis can rarely occur in rheumatoid arthritis (RA) even in the absence of systemic disease activation. The authors illustrate a female patient with well-controlled RA who presented with headaches, encephalopathy, seizures and relapsing focal neurological deficits. Primary rheumatoid cerebral vasculitis and pachymeningitis were diagnosed based on suggestive brain magnetic resonance (MR) imaging, MR angiography, cerebrospinal fluid analysis and cerebral angiography. MR showed abnormal leptomeningeal enhancement and hyperintense FLAIR signal in the cortical subarachnoid spaces consistent with pachymeningitis. Cerebral angiography findings were consistent with vasculitis. Aggressive treatment resulted in significant clinicoradiological resolution. Cerebral vasculitis is a rare but certain manifestation of RA. This complication can be diagnosed in the presence of suggestive angiographic and CSF findings. The condition may be steroid resistant, and needs to be treated more aggressively.
21598828 Association of specific amino acid sequence (QRRAA) of HLA-DRB1*0405 with rheumatoid arthr 2010 This study aimed to investigate HLA-DRB1 alleles in rheumatoid arthritis (RA) patients from Tunisia and to examine the effect of these alleles on disease severity. HLA-DRBI alleles and sub-typing of DRBI*04 and *01 were determined in 90 patients and 100 healthy controls, by PCR-SSP. HLA-DRB1*04 was significantly higher in patients (51.1%) than in controls (27%) [OR=2.83, p=0.00066]. DRBJ*0405 was found to be the unique DR4 allele associated with RA (28.88% vs 6%) [OR=6.36, p=0.000059]. A significant decrease in the frequency of HLA-DRB1*0701 was observed in RA patients (16.66%) compared to controls (36%) [p=0.0026]. However, the frequency of patients carrying the shared epitope (SE) QRRAA, was slightly increased compared with controls (37.8% vs 23%) [OR=2.03, p=0.039]. We found that the presence of rheumatoid factor, HLA-DR4 and HLA-DRBI*0405 were not significantly associated with bone erosions or the presence of extra-joint involvement. In our population, the SE (QRRAA) expressed in DRBI*04 alleles is related to the susceptibility to RA but it is not involved in RA severity in Tunisia, while DRBI*0701 might protect against this disease.
19280918 [Genome-wide association studies: recent advances and future directions]. 2009 Mar Information about human genetic variation collected by the HapMap project and recent advances in high-throughput genotyping have made genome-wide association studies (GWAS) technically feasible. In the past two years, through GWAS using commercially available SNP-typing platforms, numerous loci contributing to disease risk have been identified for common diseases including rheumatoid arthritis and systemic lupus erythematosus. From such successful studies, human geneticists have gained not only broad consensuses in methodological and technical issues, but also clear recognition about the current limitations in the common SNP-based GWAS strategy. Large-scale projects are ongoing to comprehensively catalogue genome structural variants and rare SNPs in multiple human populations. Such a deeper catalogue of genetic variation will accelerate the identification of genetic risk variants associated with common diseases.
20559723 Rheumatoid arthritis and renal light-chain deposition disease: long-term effectiveness of 2011 Sep A 68-year-old woman diagnosed with erosive rheumatoid arthritis (RA) was treated with intramuscular methotrexate 15 mg weekly and oral prednisone 5 mg daily. A favorable outcome of 6 years was followed by RA flare and nephrotic syndrome (NS). Renal biopsy revealed non-amyloid light-chain deposition disease. Laboratory analysis and bone marrow biopsy excluded monoclonal protein and plasma cell dyscrasia. Addition of subcutaneous etanercept, 25 mg twice weekly allowed rapid control of both arthritis and NS. To date, after over 7-year follow-up, RA is in clinical remission, 24-h albuminuria is consistently below 0.5 g, and serum creatinine is 0.9 mg/dl.
20609890 Radiogrammetry and radiographic absorptiometry. 2010 May Metacarpal morphometry and radiogrammetry are the oldest methods for quantitative assessment of the skeleton. The historical aspects of these measurements are reviewed. Although they were inexpensive and widely available and provided useful research and epidemiologic information, they were labor intensive and imprecise. They were replaced with the current established methods of bone mineral densitometry. With the application of modern computer vision techniques, metacarpal morphometric analysis has been rejuvenated, with improvement in precision and evidence that the method can be applied to studies in adults and children. Evidence for limited normal reference data and the ability to predict future fractures in osteoporosis and reflect activity and predict outcomes in rheumatoid arthritis are presented.
20209701 Superior forniceal advancement conjunctival pedicle (SFACP) in the management of corneal p 2010 Feb Peripheral ulcerative keratitis (PUK) is a disorder consisting of a crescent-shaped destructive inflammation of the perilimbal corneal stroma. PUK may occur in variety of systemic diseases including collagen vascular disease. We describe the outcome of superior forniceal advancement conjunctival pedicle (SFACP) in two patients with corneal perforation and impending perforation due to rheumatoid arthritis (RA) related auto immune corneal melt that has not previously been reported. Both patients had good recovery with restoration of vision when SFACP was performed as an adjunct to systemic immunosuppressive agents. SFACP is a valuable surgical option which may have an important role in reducing progression of corneal melt and underlying disease when used along with adequate systemic immunosuppressive agents.
20067446 H2S transiently blocks IL-6 expression in rheumatoid arthritic fibroblast-like synoviocyte 2010 Mar 29 Sulfur bath therapy represents the oldest form of treatment for patients with different types of rheumatic disorders. However, scientific reports about the beneficial effects of this form of therapy are controversial, rare and of poor scientific quality. Also, little is known about the role and underlying molecular mechanisms of H2S. Therefore, this topic encouraged us to investigate the influence of H2S on fibroblasts isolated from the synovial membrane of RA (rheumatoid arthritis) patients. FLSs (fibroblast-like synoviocytes) were treated with different concentrations of an exogenous H2S donor (NaHS). At defined time points, secretion of IL-6 was quantified by ELISA. Activation/deactivation of MAPKs (mitogen-activated protein kinases), p38 and p44/42 MAPK (ERK1/2) were confirmed by Western blot experiments. FLSs constitutively express and secrete large quantities of IL-6 and IL-8. Data provided prove that, in FLSs, constitutive as well as IL-1beta-induced expression of IL-6 is transiently and partially down-regulated by the short treatment of cells with low concentrations of NaHS. Another key finding is that H2S deactivates p44/42 MAPK (ERK1/2). Long-term exposure of FLSs to H2S provides stimulatory effects, leading to reinforced activation of p38 MAPK and ERK1/2 accompanied by upregulation of IL-6 expression. Presented data seem of importance for studying (patho-) physiological functions of H2S and also for re-evaluating sulfur spa therapy as one of the oldest forms of therapy for rheumatic disorders.
19351624 Increasing the infliximab dose in rheumatoid arthritis patients: a randomised, double blin 2009 Aug OBJECTIVE: To evaluate the effect of infliximab dose escalation in incomplete responders in a randomised controlled trial. METHODS: 141 rheumatoid arthritis (RA) patients treated with infliximab for 12 months (3 mg/kg; intervals 0, 2, 6 and then 8 weeks) who responded to the drug (disease activity score in 28 joints (DAS28) decrease >1.2) but who were not in remission (DAS28 >2.6) were enrolled into the study. Patients were randomly assigned into arm A, 3 mg/kg, and arm B, 5 mg/kg infliximab every 8 weeks. Outcome measures included the DAS28, its components and C-reactive protein (CRP). RESULTS: There were no significant differences in changes in the DAS28, its components, or CRP in patients in arms A and B during the 12 months of treatment. All patients showed a DAS28 decrease greater than 0.6 after 28 weeks. Eleven patients interrupted therapy in arm A and 14 in arm B. Infusion reactions and non-serious adverse events were observed in 4.2% and 28.2% of arm A patients and in 7.2% and 47.8% of arm B patients. The frequency of serious adverse events was comparable between arms A and B (16.9% and 15.9%, respectively), and the frequency of serious infections was not significantly greater in the higher dose group (5.8%) than in the lower dose group (5.6%). CONCLUSIONS: In this setting, increasing the infliximab dose from 3 mg/kg to 5 mg/kg in RA patients with residual disease activity did not improve efficacy but moderately increased toxicity. These data indicate that a switch to another biological treatment would be a more appropriate strategy in incomplete responders.
20108014 Erosive osteoarthritis: a current review of a clinical challenge. 2010 Jul Erosive osteoarthritis, a less common subtype of osteoarthritis, is often described as a more severe form. This combination of cartilage degeneration with pathologic features suggestive of inflammatory synovial changes generally manifests in women around the time of menopause and hormonal levels as well as genetics are thought to play a role in its onset. The hands are most often involved with the sudden onset of palpable pain and swelling of the distal interphalangeal joints and proximal interphalangeal joints most frequently, but other joints have been reported. Phalangeal deformities appearing as wavy or subluxed as well as Heberden and Bouchard nodes can be seen clinically. Laboratory tests for systemic inflammation are usually normal but small studies looking at markers of bone resorption have shown increased levels in these patients. Radiographs reveal central joint erosions implying an inflammatory process which has been described in synovial specimens. Treatment options that have been tried include those utilized for general osteoarthritis as well as those for rheumatoid arthritis. Since prolonged disability in hand function can occur, further studies looking at its pathogenesis and targeted treatment options are needed.
20399896 Improvement of experimental accelerated atherosclerosis by chondroitin sulphate. 2010 Jun The rheumatic diseases have been associated with accelerated atherosclerosis. Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by persistent synovial inflammation which leads to disability and structural changes in joints. Epidemiological studies have demonstrated an increased cardiovascular mortality in patients with RA. In these patients, atherosclerotic plaque occurs earlier, and it has a faster evolution than in general population. Atherosclerosis (AT) is also an inflammatory disease partly mediated by cytokines, many of them involved on chronic synovitis. Our group has developed a rabbit experimental model of AT aggravated by chronic arthritis to study inflammatory mechanisms involved on the progression of vascular lesions and their response to drugs. A preliminary study using this model suggests a beneficial effect of chondroitin sulphate (CS), a drug recommended for the treatment of osteoarthritis, in controlling AT lesions. Yet clinical trials should be conducted with this compound to address the same hypothesis in human studies.
19470150 Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load i 2009 INTRODUCTION: There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy. METHODS: Data for patients with rheumatoid arthritis (RA) (n = 58) or spondylarthropathy (SpA) (n = 28) were analyzed at baseline in comparison with controls (n = 22) and after 3 months of MTX or anti-TNF therapy for EBV load and EBV-specific IFNgamma-producing T cells in response to EBV latent-cycle and lytic-cycle peptides. RESULTS: The EBV load and the number of IFNgamma-producing T-cells after peptide stimulation were not significantly different between groups at baseline (P = 0.61 and P = 0.89, respectively). The EBV load was not significantly modified by treatment, for RA with MTX (P = 0.74) or anti-TNF therapy (P = 0.94) or for SpA with anti-TNF therapy (P = 1.00). The number of EBV-specific T cells was not significantly modified by treatment, for RA with MTX (P = 0.58) or anti-TNF drugs (P = 0.19) or for SpA with anti-TNF therapy (P = 0.39). For all patients, the EBV load and EBV-specific T cells were significantly correlated (P = 0.017; R = 0.21). For most patients, short-term exposure (3 months) to MTX or anti-TNF did not alter the EBV load or EBV-specific T-cell response but two patients had discordant evolution. CONCLUSIONS: These data are reassuring and suggest there is no short-term defect in EBV-immune surveillance in patients receiving MTX or anti-TNF drugs. However, in these patients, long term follow-up of EBV-specific T-cell response is necessary and the role of non-EBV-related mechanisms of lymphomagenesis is not excluded.
20062995 Etanercept treatment reduces the serum levels of interleukin-15 and interferon-gamma induc 2010 Apr Tumor necrosis factor-alpha (TNF-alpha) has an essential role in the pathogenesis of rheumatoid arthritis (RA) and has been known to induce the production of several inflammatory molecules in vivo. To analyze in vivo the active mechanism of the TNF-alpha blocking agent, etanercept, the serum levels of the cytokine interleukin-15 (IL-15) and the chemokines growth-regulated protein-alpha (Gro-alpha), and interferon-gamma inducible protein-10 (IP-10) in RA patients were measured. Twenty-two patients with RA were administered etanercept once or twice a week for more than 6 months. The clinical and laboratory parameters were measured and serum levels of IL-15, Gro-alpha, and IP-10 were determined using enzyme-linked immunosorbent assay (ELISA) kits at the baseline and at 3 and 6 months after the initial treatment. Additionally, the production of IL-15 and IP-10 by cultured synovial cells stimulated with TNF-alpha from RA patients was determined by ELISA. A significant decrease in serum levels of IL-15 and IP-10 was observed at 3 and 6 months after initial treatment with etanercept, but not in those of Gro-alpha. TNF-alpha induced production of IP-10, but not IL-15 in cultured synovial cells from RA patients. This study demonstrated for the first time the reduction of IP-10 and IL-15 production in RA patients as active mechanisms of etanercept.