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ID PMID Title PublicationDate abstract
12595635 Novel autoantibodies to pituitary gland specific factor 1a in patients with rheumatoid art 2003 Feb OBJECTIVE: We recently identified a new protein, pituitary gland specific factor 1a (PGSF1a), that is specifically transcribed in the pituitary gland. In our investigation of anti-PGSF1a antibody for pituitary diseases, we examined it in patients with RA and other autoimmune diseases. We unexpectedly discovered the frequent existence of anti-PGSF1a antibody in patients with RA. We therefore examined the prevalence of this antibody to understand its clinical significance in RA. METHODS: Anti-PGSF1a antibody was detected by radioligand assay using recombinant (35)S-labelled PGSF1a protein. Antibody activity is expressed as an index that was obtained by comparison with normal pooled serum. RESULTS: RA patients had a significantly higher mean anti-PGSF1a antibody index (n=46, 1.28+/-0.38, P < 0.001) than healthy controls (n=36, 1.04+/-0.13). Indices greater than the cut-off value (mean+2 S.D. of healthy controls) were found in 43.5% (20/46) and 10.0% (2/20) of patients with RA and osteoarthritis, respectively. There was no correlation between the activities of anti-PGSF1a antibodies and titres of rheumatoid factor (RF) or serum C-reactive protein concentrations, but RA patients with more erosive disease had a higher mean anti-PGSF1a antibody index. Four of eight sera samples obtained from RF-negative RA patients were positive for anti-PGSF1a antibodies. CONCLUSION: Anti-PGSF1a antibody is a useful new marker for the diagnosis of RA, especially for RF-negative RA, and may relate to clinical manifestations of RA.
15454130 Erosive osteoarthritis. 2004 Oct Erosive osteoarthritis (EOA) is believed to be a clinically uncommon subset of generalized osteoarthritis (OA) characterized by a clinical course, which is frequently aggressive. The diagnosis of EOA is accepted only for patients meeting American College of Rheumatology clinical criteria for OA of the hand and showing radiographic aspects of articular surface erosions. Conditions to be considered in the differential diagnosis include primarily nodal generalized OA, psoriatic arthritis and rheumatoid arthritis. It is possible to find erosive changes resembling EOA in endocrine diseases, microcrystal-induced diseases, chronic renal diseases, autoimmune diseases and others. Despite the absence of a clear etiology, immunogenetic studies are useful in identifying a possible predisposition to developing EOA in some subjects. No definitive therapeutic approach to EOA has been reported. It is reasonable to assume that in the presence of a symptomatic EOA our therapeutic approach should differ from that used for common, nodal, non-EOA.
15116611 Indications for patellar resurfacing in total knee arthroplasty. 2004 The management of the patella in total knee arthroplasty (TKA) traditionally has been one of three options: always resurface, never resurface, or selectively resurface the patella. Historically, implant design and surgical technique did not completely address the patellofemoral articulation. Increased understanding of patellofemoral anatomy, biomechanics, implant design, and surgical technique have led to an improvement in the previously reported high rate of patellofemoral complications associated with TKA. Traditional indications for patellar resurfacing, including age, weight, gender, patellar anatomy, quality of articular cartilage, radiographic findings, and the presence of rheumatoid arthritis deformity and preoperative anterior knee pain continue to be debated. Anterior knee pain before and after TKA must not always be presumed to be secondary to a patellofemoral resurfacing/nonresurfacing etiology, and other factors may play a role in the dynamic development of anterior knee pain after TKA. The decision to resurface the patella in TKA remains controversial, and the results of longer-term randomized controlled trials will improve understanding of this complex issue in the future.
15517622 Efficacy and safety of willow bark extract in the treatment of osteoarthritis and rheumato 2004 Nov OBJECTIVE: To investigate the efficacy and safety of a standardized willow bark extract in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: We studied 127 outpatients with hip or knee OA and a WOMAC pain score of at least 30 mm and 26 outpatients with active RA in 2 randomized, controlled, double-blind trials with followup for 6 weeks. OA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg of salicin/day, diclofenac 100 mg/day, or placebo (n = 43, 43, and 41, respectively). Main outcome measure was the pain subscore of the WOMAC OA Index. RA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg salicin/day (n = 13) or placebo (n = 13). Main outcome measure was the patient's assessment of pain rated on a 100 mm visual analog scale (VAS). RESULTS: OA trial: WOMAC pain scores decreased by 8 mm (17%) in the willow bark group and by 23 mm (47%) in the diclofenac group, compared with 5 mm (10%) in the placebo group. The difference between willow bark extract and placebo was not statistically significant (-2.8 mm; 95% CI -12.1 to 6.4 mm; p = 0.55, ANCOVA), but the difference between diclofenac and placebo was highly significant (-18.0 mm; 95% CI -27.2 to -8.8 mm; p = 0.0002, ANCOVA). RA trial: The mean reduction of pain on the VAS was -8 mm (15%) in the willow bark group compared with -2 mm (4%) in the placebo group. The difference was not statistically significant (estimated difference -0.8 mm; 95% CI -20.9 to 19.3 mm; p = 0.93, ANCOVA). CONCLUSION: The OA study suggested that the willow bark extract showed no relevant efficacy in patients with OA. Similarly, the RA trial did not indicate efficacy of this extract in patients with RA.
15033049 [Etanercept in rheumatoid arthritis patients with a poor therapeutic response to inflixima 2004 Mar 13 BACKGROUND AND OBJECTIVE: Knowing the efficacy of tumor necrosis factor alpha (TNF-alpha) antagonists infliximab or etanercept in patients with rheumatoid arthritis (RA), when one of these agents has failed, has important clinical implications. The aim of this study was to evaluate the efficacy and safety of etanercept in patients with RA, who had previously failed to infliximab. PATIENTS AND METHOD: All patients with RA of our center, who were previously treated with infliximab and then switched to etanercept for at least 6 months were included. Several clinical and biological parameters of inflammatory activity along with the disease activity index DAS-28 were assessed at baseline, after 6 weeks, at the last infusion of infliximab and after 0, 3 and 6 months on etanercept. EULAR criteria of response to therapy were used. RESULTS: Fourteen RA patients (13 females) who fulfilled the inclusion criteria were selected. These patients had been treated with infliximab for a mean (SD) of 14.6 (8.3) months when this drug was stopped. Drug withdrawal owed to inefficacy in 12 patients and to adverse events in 2 patients. Most patients achieved a satisfactory clinical response within the first months of infliximab, with a subsequent loss of the therapeutic effects in spite of an increase in the infliximab dose or a reduction of the interval between infusions. In the group of 12 patients switched to etanercept because of infliximab inefficacy, a therapeutic response was achieved in 10 (83%) of them after 6 months of etanercept therapy. The DAS-28 score (SD) improved from 5.6 (1) to 4.3 (0.8) (p = 0.019). An even better therapeutic response to etanercept was observed in those patients with an initial poor response to infliximab. No serious adverse effects were recorded during etanercept treatment. CONCLUSIONS: Etanercept is an efficient and safe therapy in RA patients when infliximab treatment has failed.
14734742 Regulation of c-Jun N-terminal kinase by MEKK-2 and mitogen-activated protein kinase kinas 2004 Feb 1 The mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK) is a critical regulator of collagenase-1 production in rheumatoid arthritis (RA). The MAPKs are regulated by upstream kinases, including MAPK kinases (MAPKKs) and MAPK kinase kinases (MAP3Ks). The present study was designed to evaluate the expression and regulation of the JNK pathway by MAP3K in arthritis. RT-PCR studies of MAP3K gene expression in RA and osteoarthritis synovial tissue demonstrated mitogen-activated protein kinase/ERK kinase kinase (MEKK) 1, MEKK2, apoptosis-signal regulating kinase-1, TGF-beta activated kinase 1 (TAK1) gene expression while only trace amounts of MEKK3, MEKK4, and MLK3 mRNA were detected. Western blot analysis demonstrated immunoreactive MEKK2, TAK1, and trace amounts of MEKK3 but not MEKK1 or apoptosis-signal regulating kinase-1. Analysis of MAP3K mRNA in cultured fibroblast-like synoviocytes (FLS) showed that all of the MAP3Ks examined were expressed. Western blot analysis of FLS demonstrated that MEKK1, MEKK2, and TAK1 were readily detectable and were subsequently the focus of functional studies. In vitro kinase assays using MEKK2 immunoprecipitates demonstrated that IL-1 increased MEKK2-mediated phosphorylation of the key MAPKKs that activate JNK (MAPK kinase (MKK)4 and MKK7). Furthermore, MEKK2 immunoprecipitates activated c-Jun in an IL-1 dependent manner and this activity was inhibited by the selective JNK inhibitor SP600125. Of interest, MEKK1 immunoprecipitates from IL-1-stimulated FLS appeared to activate c-Jun through the JNK pathway and TAK1 activation of c-Jun was dependent on JNK, ERK, and p38. These data indicate that MEKK2 is a potent activator of the JNK pathway in FLS and that signal complexes including MEKK2, MKK4, MKK7, and/or JNK are potential therapeutic targets in RA.
12530688 The adrenal hormone metabolism in the immune/inflammatory reaction. 2002 Nov The interactions between the immune system and HPA axis may be characterized by a circuit which includes; (i) activation of the HPA axis and initiation of the stress response which, in term, has immunomodulating properties; (ii) a feedback mechanism derived from the immune system which regulates the HPA axis. Over the past few years, it has become evident that the adrenal gland, itself, as the main effector organ of the HPA axis, is a major site for both the synthesis and action of numerous cytokines. In addition to the cytokine mediated activation of adrenal regulation there are cytokine independent cell-cell mediated immune-adrenal interactions. The nature of this immune-endocrine crosstalk is implicated in adrenal dysfunction and disease. During inflammatory and autoimmune disorders including sepsis, inflammatory bowel disease and rheumatoid arthritis, the immune-adrenal crosstalk becomes more critical in maintaining an adequate adrenal stress response.
12089613 [Methodology of an epidemiologic prevalence study in rheumatology: the Chiavari study]. 2002 OBJECTIVES: Goals of epidemiological studies are the description of the measures of frequency of diseases, the attempt to clarify possible etiopathogenic mechanisms, and the provision of data to support health policy decisions. To increase the familiarity of rheumatologists toward epidemiology, we describe the methodology used in a prevalence study of musculoskeletal complaints performed in Chiavari, Italy. METHODS: A questionnaire, originally developed by the Epidemiology Unit of the Arthitis Research Council in Manchester, UK, to investigate the prevalence of rheumatoid arthritis, was used after translation and validation. 4456 subjects aged 16 years or more listed in four general practices were invited to participate in the study and to fill the ARC questionnaire. The 3294 responders reported a) any past occurrence of joint swelling lasting more than four weeks and the distribution of the swollen joints on a mannequin; b) any joint pain lasting more than four weeks; c) current joint pain or swelling; d) morning stiffness; e) whether they had been previously told by a doctor they had arthritis. RESULTS: Four steps were necessary to obtain a 74% response, i.e. direct contact, two mailings and a phone interview. The performance of the different questions was good. The prevalence of the most common conditions among patients answering positively to the questions regarding morning stiffness and symmetrical swelling of joints was as follows: osteoarthritis 2.60%, fibromyalgia 1.30%, carpal tunnel syndrome 1.14%, rheumatoid arthritis 0.31%, and psoriatic arthritis 0.10%. CONCLUSIONS: Methodological issues regarding the selection of the population and sample to study, the development of a questionnaire, and the problems in obtaining valid informations are discussed.
15082494 Prevalence and impact of arthritis among nursing home residents. 2004 May OBJECTIVE: To determine the prevalence, characteristics, and impact of arthritis in the US nursing home population. METHODS: A national cross sectional sample of US nursing homes (8138 sampled residents in 1406 nursing homes) from the 1997 National Nursing Home Survey provided demographic and functional characteristics for residents with primary arthritis, any arthritis, or no arthritis diagnosis at admission. RESULTS: Of the estimated 1.6 million current nursing home residents in 1997, only 43,000 (3%) had a primary and 300,000 (19%) had any arthritis diagnosis at admission. People with a primary or any arthritis diagnosis received physical/occupational therapy, used wheelchairs and walking aids, and needed assistance with walking and transferring more often than those with no arthritis diagnosis. CONCLUSIONS: These national estimates suggest that arthritis is underreported in nursing home residents. Because arthritis contributes to an increased physical burden on staff and decreased functional capability of residents, both staff and residents can benefit from better diagnosis, intervention, and education.
12794367 [Antiphospholipid syndrome in patients with systemic connective tissue diseases]. 2003 The present study evaluates the incidence of antiphospholipid antibody syndrome (APS) in systemic rheumatic diseases patients with anticardiolipin antibodies. Clinical presentations of systemic rheumatic diseases in patients with or without APS are examined as well. The data from 242 consecutive patients suffering from rheumatoid arthritis (158 pts), systemic erythematoid lupus (53 pts), or systemic sclerosis (31 pts) are studied. Enzyme immunoassay test for IgG-anticardiolipin antibodies was performed for all patients. The IgG-anticardiolipin antibodies were found in 38 (15.7%) patients. There were 16 (30.2%) patients in erythematoid lupus group, 9 (29%) patients in systemic sclerosis group, and 13 (8.2%) patients in rheumatoid arthritis group. The diagnosis of secondary APS according to classificational criteria (1998) was confirmed in 14 (36.8%) from 38 seropositive patients: ten patients (62.5%) in lupus group, 2 (22.2%) patients in systemic sclerosis group, and 2 (15.4%) patients in rheumatoid arthritis group were found as APS patients. The majority of these patients were female (92.9%). These patients were younger as compared with systemic rheumatic diseases patients without APS (p=0.005). There was no significant difference found between APS patients and patients without APS in respect to neither duration of primary disease, nor disease activity, nor course of the disease. There were significantly more cases of fibrotic heart valves (p=0.028), and thrombocytopenia (p=0.002), and livedo reticularis (p=0.058) in APS group.
14644855 Quality of life and work in patients with rheumatoid arthritis and ankylosing spondylitis 2003 Dec OBJECTIVE: To investigate the relationship between work and quality of life (QOL) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) aged 16-59. METHODS: 1056 patients with RA and 658 with AS were included in the study. Data were obtained by postal questionnaire, which included several generic and disease related QOL instruments. Separate dimensions and physical and mental summary scores from the SF-36 were compared. Stepwise multiple regression was performed to study the relationship between work and physical and mental health related QOL, including disease related factors, coping, and fatigue. RESULTS: Physical health related QOL was reported to be worse, and mental health related QOL better, in RA than in AS in people of working age. No differences between RA and AS were found in somatic pain, physical role functioning, social functioning, emotional role functioning, vitality, or general health perception; nor were there any significant differences in fatigue and behavioural coping styles. Work was positively associated with physical health related QOL in both groups and, after disease characteristics, was the most important determinant. No association was found with mental health related QOL. CONCLUSIONS: Although physical health related QOL was worse in patients with RA, the impact on several dimensions of health related QOL in patients with RA and AS of working age under rheumatological care was comparable. Patients with RA and AS experienced similar limitations in physical role functioning, including work. Work is an important independent external determinant of physical health related QOL, but not of mental health related QOL.
12504237 [Treatment of rheumatoid arthritis by interleukin-1 receptor antagonist]. 2002 Dec PURPOSE: Interleukin -1 receptor antagonist ( IL-1Ra ) is a new option among biotherapies against rheumatoid arthritis ( RA ). THE AIM: of this review is to recall the rationale of use of IL-1Ra and to analyse the results available in the current literature. CURRENT KNOWLEDGE AND KEY POINTS: Pathophysiological data of RA give a specific position for IL-1 as a potential target for immunotherapy in this disease, confirmed in animal models. Phase II and III studies with IL-1Ra (Anakinra) demonstrated clinical efficacy versus placebo (42% responders in ACR 20 in Anakinra + methotrexate, and 23% in the placebo + methotrexate group at 24 weeks) and a structural effect (slowing of radiological progression at six months). Anakinra has obtained an European license and is indicated in RA not controlled by methotrexate, in daily subcutaneous administration (100 mg/day), in combination with methotrexate. Tolerance is fair; the most frequent side effect is represented by injection site reactions. FUTURE PROSPECTS AND PROJECTS: This ambulatory biotherapy offers new perspectives in combination with other slow acting drugs as well as biologic agents such as anti-TNF, currently under evaluation.
11850612 [Adult onset Still's disease]. 2002 Feb Adult onset Still's disease (AOSD), the adult variant of the systemic form of the juvenile rheumatoid arthritis, is an uncommon disorder of unknown origin. Although the pathogenesis has not yet been clarified, an immunologically mediated inflammation occurs in active AOSD. High spiking fever, evanescent maculo-papular skin rash, arthralgias/arthritis, neutrophilic leukocytosis, negative rheumatoid factor and antinuclear antibodies, as well as a marked hyperferritinemia are the major features of AOSD. Sore throat, lymphadenopathies, hepato-splenomegaly, abdominal pain, polyserositis, respiratory distress syndrome, multiple organ dysfunction and disseminated intravascular coagulation may also occur. The clinical course of AOSD is extremely variable and unpredictable and can be divided into three main patterns: a self-limited or monocyclic pattern, a polycyclic or intermittent course, with one or more flares of the disease and complete remission among the episodes, and a chronic course, characterized by persistently active disease, usually due to a chronic, destructive arthritis. Since there are not pathognomonic laboratory parameters or histological findings, the diagnosis of AOSD requires the exclusion of infectious, malignant and autoimmune disorders. Some sets of criteria for classification have been proposed, but so far not validated. The prognosis of AOSD is usually considered relatively benign, although a destructive arthritis may cause severe disability and the multisystemic life-threatening complications of the disease may determine a fatal outcome. Treatment usually consists in nonsteroidal anti-inflammatory drugs and corticosteroids, but a more aggressive approach with disease modifying antirheumatic or immunosuppressive drugs may be required.
12525377 Angiopoietin-1 is expressed in the synovium of patients with rheumatoid arthritis and is i 2003 Feb OBJECTIVES: To examine the potential role of the angiogenic growth factor angiopoietin-1 (Ang-1) in inflammatory arthritis. METHODS: Eighteen synovial tissue samples were obtained from 17 patients with a clinical diagnosis of rheumatoid arthritis (RA) and compared with six synovial tissue samples from six patients with osteoarthritis (OA). Ang-1 expression in synovial tissues was determined by immunohistochemistry and in situ hybridisation. Ang-1 mRNA and protein expression were also examined by northern blot analysis and enzyme linked immunosorbent assay (ELISA) in cultured synovial fibroblasts and human umbilical vein endothelial cells (HUVECs) before and after treatment with tumour necrosis factor (TNF)alpha. RESULTS: Ang-1 protein expression was detected by immunohistochemistry in 16/18 RA synovial tissue samples. Ang-1 protein was frequently observed in the synovial lining layer and in cells within the sublining synovial tissue, in both perivascular areas and in areas remote from vessels. In contrast, Ang-1 was only weakly detected in these sites in OA samples. Ang-1 mRNA and protein were also expressed in cultured synovial fibroblasts derived from patients with RA. In addition, induction of Ang-1 mRNA and protein was observed by northern blot analysis and ELISA after stimulation of RA synovial fibroblasts, but not HUVECs, with the proinflammatory cytokine TNF alpha. CONCLUSIONS: Ang-1 mRNA and protein are expressed in the synovium of patients with RA, and are up regulated in synovial fibroblasts by TNF alpha. Ang-1 may therefore be an important regulator of angiogenesis in inflammatory arthritis.
14534829 Primary Stanmore total hip arthroplasty with increased cup loosening in rheumatoid patient 2003 We studied all Stanmore total hip arthroplasties (THA, n=325) implanted at our center between 1980 and 1990. Seven patients (seven hips), followed for less than 12 months, were excluded. Five hips were lost at follow-up. The mean follow-up was 117 (12-252) months. A total of 18 hips were revised, with median time between operation and revision 163 months. With revision as endpoint, a survival rate analysis was calculated. The mean survival for all hips was 82% at 18 years (95% confidence interval 64-101%). For hips with rheumatoid arthritis, the survival rate was 58%, whereas in osteoarthritic hips the rate was 95% after 18 years. A high proportion of acetabular loosening was seen in rheumatoid hips.
15603880 Discordant expression of HLA class II-associated co-chaperones and HLA-DRB alleles in cult 2004 Dec Human leukocyte antigen (HLA)-DR-positive synovial fibroblasts are frequently observed in rheumatoid arthritis (RA) and may be implicated in the autoimmune reaction because RA is associated with certain HLA-DRB1* alleles. The question of whether components of the class II antigen presentation pathway and specific DRB alleles are efficiently expressed by synovial fibroblasts is germane to this hypothesis. To address this, cultured fibroblast-like synoviocytes (cFLS) were analyzed for constitutive and interferon (IFN)-gamma-induced expression of specific DRB alleles and class II-associated cochaperones. IFN-gamma induction of invariant chain, DM, and DR molecules was observed in all cFLS, but expression of specific DR allotypes was variable. Interestingly, DM-modulated epitopes on RA-associated DR molecules were either absent or delayed, despite strong DM expression and a paucity of major histocompatibility complex/class II-associated invariant chain peptide complexes. Altered expression of specific peptide-dependent epitopes on RA-associated HLA-DR molecules suggests differences in antigen presentation by cFLS, which may have implications for the immunopathogenesis of RA.
15291252 [Collagen diseases with opportunistic infections]. 2004 Jun Treatment of opportunistic infections emerging in collagen diseases is very important as well as the therapy of original diseases. Lung tuberculosis, Pneumocystis carinii and lung fungal infections are main opportunistic infections. There is effective prophylaxis against them, though the cases for their administration should be carefully chosen because of their adverse effects. We have administrated INH and ST (Sulphomethoxazole and Trimethoprim) more than 15 years as the prophylaxis against tuberculosis and P. carinii to the cases who are treated more than 60 mg of prednisolone per day as an initial dose until less than 30 mg per day and completely succeeded. Infliximab treatment has been reported that it often induces tuberculosis in abroad and lots of occurrence was anticipated in Japan where high incidence of tuberculosis is observed. So far, however, there are only few patients, maybe due to the selection of the patients and actively utilizing prophylaxis.
15293088 Systematic review of primary total elbow prostheses used for the rheumatoid elbow. 2004 Aug Total elbow prosthesis (TEP) has been shown to be a viable option for treatment of the rheumatoid elbow. Many types of TEP have been studied, but the heterogeneity of the studies makes most conclusions subject to discussion. The aim of this systematic review is to show the differences between the most commonly used TEP for the destroyed rheumatoid elbow. After a search in Pubmed (NLM, Bethesda, USA) the senior author selected eight frequently used TEP: the Capitellocondylar, Coonrad-Morrey, GSB III, Kudo, Liverpool, Norway, Roper-Tuke and Souter-Strathclyde. For inclusion studies we arbitrarily formulated nine criteria, after which clearly adverse events were defined for comparison purposes. The Capitellocondylar and Souter-Strathclyde prostheses are the most-studied treatments for replacing the rheumatoid elbow. In contrast to the Capitellocondylar, the Souter-Strathclyde prosthesis showed higher loosening rates but implemented modifications of the design have reduced these rates in recent studies. Nevertheless, in relation to most other joint replacements in rheumatoid patients, all TEP still have higher complication rates. For this reason an elbow prosthesis may just be warranted in seriously disabled patients.
11908556 High levels of interleukin 13 in rheumatoid arthritis sera are modulated by tumor necrosis 2002 Mar OBJECTIVE: To investigate the physiology of interleukin 13 (IL-13) in rheumatoid arthritis (RA) and the effects of tumor necrosis factor (TNF) antagonists (etanercept) on the distribution of IL-13 in patients with RA. METHODS: We measured cytokine levels in RA sera (pre/post etanercept), RA synovial fluid (SF), osteoarthritis (OA) SF, and normal human sera by ELISA. Detection of IL-13 was not influenced by rheumatoid factor, as revealed in spike recovery and isotype antibody control studies. Biologically active IL-13 in RA SF was studied using dendritic cell (DC) progenitors that develop into mature DC with IL-13 and with neutralizing antibodies to IL-13. The modulation of IL-13 by etanercept was compared to that of IL-6 and monocyte colony stimulating factor (M-CSF). The effect of etanercept on the ability of RA sera to promote DC growth was studied using DC progenitors. RESULTS: IL-13 was increased in RA sera versus normal sera, OA SF, and RA SF. Relative to OA SF and normal sera, RA SF was enriched in IL-13. The IL-13 contained in RA samples was biologically active, prompting DC growth from progenitors. Circulating DC growth activity was strongly reduced by anti-TNF therapy. Whereas decreases in DC growth factors including IL-13 and IL-6 occurred with etanercept therapy and were associated with clinical improvement, concurrent increases in circulating M-CSF (a non-DC, monocyte-specific growth factor) were noted. CONCLUSION: The increase of biologically active IL-13 in RA supports the concept that IL-13 regulates immune cell (including dendritic cell) activity and indicates how the varied anatomical distribution of cytokines may play a role in the RA disease process. The differential regulation of circulating IL-13 and M-CSF levels by TNF antagonists further implies discrete roles in the TNF-cytokine network in RA.
14613266 Coffee consumption and risk of rheumatoid arthritis. 2003 Nov OBJECTIVE: Recent reports have suggested an association between consumption of coffee or decaffeinated coffee and the risk of rheumatoid arthritis (RA), although data are sparse and somewhat inconsistent. Furthermore, existing studies measured dietary exposures and potential confounders only at baseline and did not consider possible changes in diet or lifestyle over the followup period. We studied whether coffee, decaffeinated coffee, total coffee, tea, or overall caffeine consumption was associated with the risk of RA, using the Nurses' Health Study, a longitudinal cohort study of 121,701 women. METHODS: Information on beverage consumption was assessed with a food frequency questionnaire (FFQ) that was completed every 4 years, from baseline in 1980 through 1998. Among the 83,124 women who completed the FFQ at baseline, the diagnosis of incident RA (between 1980 and 2000) was confirmed in 480 women by a connective tissue disease screening questionnaire and medical record review for American College of Rheumatology criteria. Relationships between intake of various beverages and the risk of RA were assessed in age-adjusted models and in multivariate Cox proportional hazards models including the cumulative average intake of each beverage during the followup period, adjusted for numerous potential confounders. In addition, for direct comparisons with prior reports, multivariate analyses were repeated using only baseline beverage information. RESULTS: We did not find a significant association between decaffeinated coffee consumption of >/=4 cups/day (compared with no decaffeinated coffee consumption) and subsequent risk of incident RA, in either an adjusted multivariate model (relative risk [RR] 1.1, 95% confidence interval [95% CI] 0.5-2.2) or a multivariate model using only baseline reports of decaffeinated coffee consumption (RR 1.0, 95% CI 0.6-1.7). Similarly, there was no relationship between cumulative caffeinated coffee consumption and RA risk (RR 1.1, 95% CI 0.8-1.6 for >/=4 cups per day versus none) or between tea consumption and RA risk (RR 1.1, 95% CI 0.7-1.8 for >3 cups/day versus none). Total coffee and total caffeine consumption were also not associated with the risk of RA. CONCLUSION: In this large, prospective study, we find little evidence of an association between coffee, decaffeinated coffee, or tea consumption and the risk of RA among women.