Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 16755040 | F1 hybrid mice (BALB/c x DBA/1) are resistant to collagen-induced arthritis with beta-gluc | 2006 Jun | Collagen-induced arthritis (CIA) is an experimental model of rheumatoid arthritis (RA) used for studying the clinical, immunological and genetic factors of the disease. Many studies of genetic susceptibility to CIA have been performed, usually with two strains of mice, DBA/1 and B10.RIII, since they are highly susceptible to CIA. Furthermore, F1 hybrid mice of susceptible and resistant strains reportedly develop arthritis. Recently, we reported that particles of beta-glucan, OX-CA, prepared from Candida albicans by NaClO-oxidation, acted as an adjuvant for CIA. Although, there have been many studies about the relationship between antigen and the major histocompatibility complex (MHC) in F1 hybrid mice, little is known argument about susceptibility to adjuvants. Therefore, we checked the susceptibility of F1 hybrids to CIA using OX-CA as an adjuvant. BALB/c and DBA/1 were mated to generate F1 hybrids which were then immunized with type II collagen (CII) plus Freund's complete adjuvant (FCA) or OX-CA. The results showed that F1 hybrids injected with CII plus FCA developed severe arthritis at an incidence ratio 80%, versus only 20% in mice injected with CII plus OX-CA. Furthermore, levels of anti-CII antibody, especially of the IgG2a subclass, in sera from mice treated with CII plus OX-CA were significantly low. Susceptibility to CIA might depend on not only MHC but also the adjuvant used for immunoactivation. | |
| 18360651 | Infliximab (Remicade) in the treatment of psoriatic arthritis. | 2006 Dec | Elucidation of the cellular immunopathology and cytokine profile of psoriatic arthritis (PsA), a chronic inflammatory disease associated with psoriasis, has resulted in the development of a number of novel biologic therapies. Among these biologics, tumor necrosis factor-alpha (TNF-alpha) inhibitors have been used successfully to treat patients suffering from rheumatoid arthritis or psoriasis. The pivotal role of TNF-alpha in the pathogenesis and progression of PsA suggested that anti-TNF-alpha agents could be effective in controlling PsA. The results from two large, randomized, double-blind, placebo-controlled trials in patients with moderate to severe PsA indicated that the anti-TNF-inhibitor, infliximab, can control both the joint and skin manifestations of the disease. This review focuses on the clinical development of infliximab as a treatment for PsA. The development of other anti-TNF-alpha biologics is also discussed. | |
| 27157079 | PET Imaging of Arthritis. | 2006 Apr | Fluorodeoxyglucose (FDG) PET imaging of arthritis is still in its infancy. Neither the optimal methodology nor the real clinical value is known at this time. Nevertheless, initial results are highly encouraging and the feasibility of the technique is demonstrated. PET findings are correlated with results obtained with state-of-the-art MRI and ultrasonography as well as with established clinical assessment of rheumatoid arthritis. There are indications that FDG-PET may provide unique information regarding the prognosis and early response to treatment. The mechanism of FDG uptake in the diseased joints has to be clarified further, but the available data indicate that it is well suited for imaging inflammatory joint disorders and, possibly, osteoarthritis. What lies ahead is the important work of clinical validation to verify the diagnostic and prognostic accuracy before envisioning a clinical role in routine practice. | |
| 16239386 | What are the roles of metalloproteinases in cartilage and bone damage? | 2005 Nov | A role for metalloproteinases in the pathological destruction in diseases such as rheumatoid arthritis and osteoarthritis, and the irreversible nature of the ensuing cartilage and bone damage, have been the focus of much investigation for several decades. This has led to the development of broad spectrum metalloproteinase inhibitors as potential therapeutics. More recently it has been appreciated that several families of zinc dependent proteinases play significant and varied roles in the biology of the resident cells in these tissues, orchestrating development, remodelling, and subsequent pathological processes. They also play key roles in the activity of inflammatory cells. The task of elucidating the precise role of individual metalloproteinases is therefore a burgeoning necessity for the final design of metalloproteinase inhibitors if they are to be employed as therapeutic agents. | |
| 17131799 | [Polymyalgia rheumatica]. | 2006 Sep 17 | Polymyalgia rheumatica is a disorder that affects people over 50 years of age. The etiology of the disease has not been hitherto clarified exactly. Its incidence among people over 50 is in the range of 0.1-0.5%. The incidence rate peaks in the age group of 60-70 years. It is also found in younger people, but far less frequently. The diagnosis is based primarily on locomotor complains--namely on pronounced pain, morning stiffness of the shoulder girdle, pelvic girdle and neck. Complaints relating to the arms and legs (such as muscular weakness, oedema, tendonitis etc.) are also observed, however, in one third of the cases. The diagnostic criteria are defined empirically. Polymyalgia rheumatica was formerly considered to be a form of elderly onset rheumatoid arthritis. The progressive erosion process is absent in the case of polymyalgia rheumatica unlike in the case of rheumatoid arthritis. Numerous factors are known, which point to a link between polymyalgia rheumatica and giant cell vasculitis, arthritis, but the precise nature of this relationship remains unknown. Both conditions affect the same age group in the general population and they are even found--not infrequently--in the same patient. Polymyalgia rheumatica can be found in 40% of the patients suffering from arthritis while the histological examination detected mild vasculitis in approximately 10% of the patients suffering for "isolated" polymyalgia rheumatica. The response to be given to the acute phase is similar in both disorders. Scandinavian authors consider polymyalgia rheumatica as the appearance of generalised arthritis. Arthroscopic, nuclear magnetic resonance imaging as well as isotopic studies show unequivocally, that in the background of the osteo-muscular symptoms, complaints, inflammation is to be found partly of the joints but primarily that of the periarticular synovial structures. The above mentioned--dominant--proximal symptoms can often mask the distal locomotor disorders (pitting oedema of the hands and feet, tendonitis, tendosynovitis, carpal tunnel syndrome). The disorder may be accompanied by atypical generalised symptoms (loss of appetite, weight loss, fever, fatigue). An excellent indicators of the acute phase reactions are erythrocyte sedimentation rate, C-reactive protein and interleukin-6. These are suitable for monitoring the effectiveness of the therapy, for indicating a relapse/recurrence. It should be noted, that polymyalgia rheumatica may also be present if the erythrocyte sedimentation rate and C-reactive protein values are low. This disorder is also characterised by fast and effective response to corticosteroid, which should be administered for 1-2 years. In some individual cases a different dosage regime may be necessary: steroid administered in low dosage over a longer period of time. Administration of methotrexate and anti-tumor necrotic factor-alpha may also be considered as alternative or adjuvant therapy for lowering the quantity of corticosteroid. Further multicenter, double blind studies should, however, be performed on large number of patients in this regard. | |
| 16228217 | Incidence and outcomes of uveitis in juvenile rheumatoid arthritis, a synthesis of the lit | 2006 Mar | BACKGROUND: Juvenile rheumatoid arthritis (JRA) is the most common systemic cause of pediatric uveitis in Europe and North America. Uveitis is commonly perceived as a frequent sequela of JRA and JRA-associated uveitis is commonly considered to have a complicated course with frequent adverse visual outcomes. METHODS: We performed a systematic literature search for series of consecutive patients with JRA (as defined by the American College of Rheumatology criteria) reporting on the frequency of uveitis and/or complications of uveitis, published between January 1980 and December 2004. The main outcome measures were: the cumulative incidence of uveitis in JRA, the cumulative incidence of adverse visual outcome and that of complications in JRA-associated uveitis. Additionally, the influence of gender, presence of antinuclear antibody (ANA) and disease onset subtype to the likelihood of developing uveitis were examined. RESULTS: Analysis of pooled data from the 26 eligible series suggested a cumulative incidence of uveitis in JRA of 8.3% [95% confidence intervals (CI), 7.5-9.1%]. The cumulative incidence of uveitis varied according to geographic location, being highest in Scandinavia, then the US, then Asia and lowest in India. JRA-associated uveitis was more common in pauciarticular than polyarticular onset patients [odds ratio (OR) = 3.2, 95% CI, 2.33-4.36] and in ANA-positive than ANA-negative patients (OR = 3.18, 95% CI, 2.22-4.54). Female gender was only a weak risk factor for the development of uveitis in JRA patients (OR = 1.69, 95% CI 1.09-2.62) and was not statistically significant after considering disease onset subtypes. In JRA-associated uveitis the cumulative incidence of cumulative incidence of adverse outcome (visual acuity < 20/40 OU) was 9.2% (95% CI: 4.7-15.8) of cataracts 20.5% (95% CI: 15.5-26.3), of glaucoma 18.9% (95% CI: 14.4-24.2) and of band keratopathy 15.7% (95% CI: 10.9-21.7). CONCLUSION: The cumulative incidence of uveitis in JRA varies according to geographic location, presence of ANA, type of JRA onset and gender. Uveitis, adverse visual outcome, and complications in JRA are less frequent than commonly accepted. | |
| 15927377 | Nerve growth factor mediates hyperalgesia and cachexia in auto-immune arthritis. | 2005 Jul | Pain and cachexia are two of the most debilitating aspects of rheumatoid arthritis. Despite that, the mechanisms by which they are mediated are not well understood. We provide evidence that nerve growth factor (NGF), a secreted regulatory protein that controls neuronal survival during development, is a key mediator of pain and weight loss in auto-immune arthritis. Function blocking antibodies to NGF completely reverse established pain in rats with fully developed arthritis despite continuing joint destruction and inflammation. Likewise, these antibodies reverse weight loss while not having any effect on levels of the pro-cachectic agent tumor necrosis factor (TNF). Taken together, these findings argue that pathological joint pain and joint destruction are mechanistically independent processes and that NGF regulates an alternative cachexia pathway that is independent or downstream of TNF. | |
| 16652429 | Clinical significance of decreased serum concentration of cartilage oligomeric matrix prot | 2006 May | OBJECTIVE: Serum cartilage oligomeric matrix protein (COMP) concentration is elevated in patients with early osteoarthritis and early rheumatoid arthritis, and may be a biomarker of cartilage turnover. We investigated whether serum COMP concentration could be a clinically significant marker of arthritis and/or growth impairment in juvenile idiopathic arthritis (JIA). METHODS: Specimens were collected from 82 healthy blood donors under 22 years of age with no growth impairment who served as healthy controls, and from 24 patients with JIA (6 with oligoarthritis, 10 with polyarthritis, 8 with systemic JIA) presenting with active arthritis. Serum COMP concentration was determined using a human COMP assay kit. RESULTS: Serum COMP concentrations were significantly higher in all controls less than 16 years of age than in all controls aged 16 years or older. There was a significant negative correlation between serum COMP concentration and serum C-reactive protein in patients with JIA. Serum COMP concentrations in patients with systemic JIA were significantly lower than those in controls. CONCLUSION: Serum COMP concentrations in healthy children reflected increased cartilage turnover in the growth phase. Because the serum COMP concentration was decreased in cases of systemic JIA in which growth impairment was pronounced, the systemic inflammation occurring in systemic JIA may have an effect on cartilage turnover, which plays an important role in growth. Serum COMP concentration may prove to be a marker that indicates growth impairment in systemic JIA. | |
| 17282480 | Automated classification schemes for optical tomographic arthritis scans. | 2005 | We have recently developed a sagittal laser optical tomographic (SLOT) imaging system for the diagnosis and monitoring of inflammatory processes in proximal interphalangeal (PIP) joints of patients with rheumatoid arthritis (RA). While cross sectional images of distribution of optical properties can now be generated easily, clinical interpretation of these images remains a challenge. In this paper, we apply and analyse two machine learning methods for optimal identification and severity classification of RA in a data set of 78 joints. The methods surveyed include Fisher Face with Support Vector Machines (SVMs), and Transformed Mixtures of Gausians (TMG). It appears that TMG methods outperform the approach using Fisher Face with SVMs; however, the results need to be further validated in studies involving larger patient populations. | |
| 16485060 | Etanercept for the treatment of psoriasis. | 2006 Feb | Etanercept has recently been approved for the treatment of moderate-to-severe plaque psoriasis at a dose of 50mg twice per week for 12 weeks followed by a maintenance dose of 50mg once weekly thereafter. Clinical studies have shown excellent efficacy and a good safety profile in patients with psoriasis. Extensive information on etanercept safety is available as this biological agent has been used for many years for other indications such as rheumatoid arthritis, and psoriatic arthritis. | |
| 15868633 | Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthri | 2005 May | OBJECTIVE: . To assess the efficacy and safety of etanercept in a large cohort of children with refractory systemic onset juvenile rheumatoid arthritis (SOJRA). METHODS: Standardized questionnaires were sent to US pediatric rheumatologists about patients with SOJRA treated with etanercept. Data were collected at baseline and at the last visit on etanercept. Response to treatment was assessed and compared to baseline as the mean percentage reduction in the following: acute phase reactants, prednisone dose, active joint count, and physician global assessment of disease activity. Response was defined as poor if the mean reduction was < 30%, fair if 30% to < 50%, good if 50% to < 70%, and excellent if > 70%. RESULTS: We analyzed data obtained by survey of 82 SOJRA patients treated with etanercept for a mean of 25 months. Poor response to treatment was observed in 45% of the children, fair response in 9%, good in 13%, and excellent in 33%. Baseline steroid therapy could be discontinued in 27/59 (46%) patients. One or more disease flares occurred in 45% of all patients. Twenty-nine patients (35%) discontinued therapy, mostly due to lack of response or flare. There were 32 adverse event reports, most not considered serious, except for 2 cases of macrophage activation syndrome. CONCLUSION: In this cohort of children with SOJRA, 46% had a good or excellent response, and most were able to reduce concomitant corticosteroid doses. The response to etanercept was fair or poor in more than half our study population, and disease flares were common. Due to the unique cytokine profile of SOJRA, tumor necrosis factor blockade may not be the optimal therapeutic approach for children with treatment-resistant SOJRA. | |
| 17016504 | Pharmacological blockade of CCR1 ameliorates murine arthritis and alters cytokine networks | 2006 Nov | BACKGROUND AND PURPOSE: The chemokine receptor CCR1 is a potential target for the treatment of rheumatoid arthritis. To explore the impact of CCR1 blockade in experimental arthritis and the underlying mechanisms, we used J-113863, a non-peptide antagonist of the mouse receptor. EXPERIMENTAL APPROACH: Compound J-113863 was tested in collagen-induced arthritis (CIA) and three models of acute inflammation; Staphylococcus enterotoxin B (SEB)-induced interleukin-2 (IL-2), delayed-type hypersensitivity (DTH) response, and lipopolysaccharide (LPS)-induced tumour necrosis factoralpha (TNFalpha) production. In the LPS model, CCR1 knockout, adrenalectomised, or IL-10-depleted mice were also used. Production of TNFalpha by mouse macrophages and human synovial membrane samples in vitro were also studied. KEY RESULTS: Treatment of arthritic mice with J-113863 improved paw inflammation and joint damage, and dramatically decreased cell infiltration into joints. The compound did not inhibit IL-2 or DTH, but reduced plasma TNFalpha levels in LPS-treated mice. Surprisingly, CCR1 knockout mice produced more TNFalpha than controls in response to LPS, and J-113863 decreased TNFalpha also in CCR1 null mice, indicating that its effect was unrelated to CCR1. Adrenalectomy or neutralisation of IL-10 did not prevent inhibition of TNFalpha production by J-113863. The compound did not inhibit mouse TNFalpha in vitro, but did induce a trend towards increased TNFalpha release in cells from synovial membranes of rheumatoid arthritis patients. CONCLUSIONS AND IMPLICATIONS: CCR1 blockade improves the development of CIA, probably via inhibition of inflammatory cell recruitment. However, results from both CCR1-deficient mice and human synovial membranes suggest that, in some experimental settings, blocking CCR1 could enhance TNF production. | |
| 17007638 | CD97 neutralisation increases resistance to collagen-induced arthritis in mice. | 2006 | Synovial tissue of rheumatoid arthritis (RA) patients is characterised by an influx and retention of CD97-positive inflammatory cells. The ligands of CD97, CD55, chondroitin sulfate B, and alpha5beta1 (very late antigen [VLA]-5) are expressed abundantly in the synovial tissue predominantly on fibroblast-like synoviocytes, endothelium, and extracellular matrix. Based upon this expression pattern, we hypothesise CD97 expression to result in accumulation of inflammatory cells in the synovial tissue of RA patients. To determine the therapeutic effect of blocking CD97 in an animal model of RA, collagen-induced arthritis was induced in a total of 124 DBA/J1 mice. Treatment was started on day 21 (early disease) or on day 35 (longstanding disease) with the blocking hamster anti-mouse CD97 monoclonal antibody (mAb) 1B2, control hamster immunoglobulin, or NaCl, applied intraperitoneally three times a week. The paws were evaluated for clinical signs of arthritis and, in addition, examined by radiological and histological analysis. Mice receiving 0.5 mg CD97 mAb starting from day 21 had significantly less arthritis activity and hind paw swelling. Furthermore, joint damage and inflammation were reduced and granulocyte infiltration was decreased. When treatment was started on day 35, CD97 mAb treatment had similar effects, albeit less pronounced. The results support the notion that CD97 contributes to synovial inflammation and joint destruction in arthritis. | |
| 15723739 | Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. | 2005 Feb | OBJECTIVE: This study evaluated whether supplementation with olive oil could improve clinical and laboratory parameters of disease activity in patients who had rheumatoid arthritis and were using fish oil supplements. METHODS: Forty-three patients (34 female, 9 male; mean age = 49 +/- 19y) were investigated in a parallel randomized design. Patients were assigned to one of three groups. In addition to their usual medication, the first group (G1) received placebo (soy oil), the second group (G2) received fish oil omega-3 fatty acids (3 g/d), and the third group (G3) received fish oil omega-3 fatty acids (3 g/d) and 9.6 mL of olive oil. Disease activity was measured by clinical and laboratory indicators at the beginning of the study and after 12 and 24 wk. Patients' satisfaction in activities of daily living was also measured. RESULTS: There was a statistically significant improvement (P < 0.05) in G2 and G3 in relation to G1 with respect to joint pain intensity, right and left handgrip strength after 12 and 24 wk, duration of morning stiffness, onset of fatigue, Ritchie's articular index for pain joints after 24 wk, ability to bend down to pick up clothing from the floor, and getting in and out of a car after 24 wk. G3, but not G2, in relation to G1 showed additional improvements with respect to duration of morning stiffness after 12 wk, patient global assessment after 12 and 24 wk, ability to turn faucets on and off after 24 wk, and rheumatoid factor after 24 wk. In addition, G3 showed a significant improvement in patient global assessment in relation to G2 after 12 wk. CONCLUSIONS: Ingestion of fish oil omega-3 fatty acids relieved several clinical parameters used in the present study. However, patients showed a more precocious and accentuated improvement when fish oil supplements were used in combination with olive oil. | |
| 16614989 | Increased frequency of mutations in the gene responsible for familial Mediterranean fever | 2006 Apr | The MEFV gene, responsible for familial Mediterranean fever (FMF), is involved in inflammatory reactions through altered leukocyte apoptosis, secretion of interleukin (IL)-1beta, and activation of the NF-kappa B pathway. Ulcerative Colitis (UC) and FMF are both characterized by a recurrent pattern of presentation with periods of remission and flares associated with neutrophilic infiltration at the site of injury. The aim of this study was to investigate the possible correlation between UC and MEFV gene alterations. Twenty-five consecutive, first-diagnosed and untreated UC patients, 28 control patients with rheumatoid arthritis, and 65 normal individuals were analyzed. Nonisotopic RNase Cleavage Assay (NIRCA) was applied as a first-step mutational screening method of exons 10 and 2 of MEFV gene; direct sequencing was subsequently performed to confirm the results. MEFV mutations were identified in 7 (3 M694V/0, 2 M680I/0, 1 E148Q/E148Q, and 1 A744S/0) out of 25 UC patients versus 1 (M694V/0) out of 28 rheumatoid arthritis patients (P = .0199) and 1 (M694V/0) out of 65 healthy controls (P = .0004). Four out of 7 patients with MEFV mutations had inflammatory arthritis, a clinical finding that was not observed in the 18 UC patients with unmutated MEFV (P = .0028). Patients with UC almost universally carried the T A C G MEFV exon 2 haplotype in contrast with normal individuals (P < .0001) and FMF patients (P = .0310). In conclusion the increased frequency of mutations of MEFV in UC patients, especially in those with episodic arthritis, suggests a possible modifying effect of MEFV in the disease process and its localization within the joint. The difference in distribution of MEFV exon 2 haplotypes between UC patients and both FMF patients and normal individuals, suggests that UC patients constitute a genetically distinct population. Larger, longitudinal studies are needed to confirm these initial findings. | |
| 17149059 | Peripheral neuropathies associated with rheumatoid synovial cysts of the elbow joint: thre | 2006 Dec | We present 3 cases with peripheral neuropathies of the median, posterior interosseous, and ulnar nerves associated with rheumatoid synovial cysts of the elbow joint. Magnetic resonance imaging and electrophysiological examination led to the final diagnosis of the relation to synovial cysts of the elbow joint. All patients underwent surgical decompression of these nerves and synovectomy of the elbow joint. Functional recovery was excellent in the 2 patients with median and posterior interosseous nerve palsy but incomplete in the patient with ulnar nerve palsy. Such neuropathies require consideration in the differential diagnosis of wrist and hand disability in patients with rheumatoid arthritis. This awareness should enhance early diagnosis and treatment by surgical decompression. | |
| 15987485 | Osteoporosis in experimental postmenopausal polyarthritis: the relative contributions of e | 2005 | Generalized osteoporosis in postmenopausal rheumatoid arthritis (RA) is caused both by estrogen deficiency and by the inflammatory disease. The relative importance of each of these factors is unknown. The aim of this study was to establish a murine model of osteoporosis in postmenopausal RA, and to evaluate the relative importance and mechanisms of menopause and arthritis-related osteoporosis. To mimic postmenopausal RA, DBA/1 mice were ovariectomized, followed by the induction of type II collagen-induced arthritis. After the mice had been killed, paws were collected for histology, one femur for bone mineral density (BMD) and sera for analyses of markers of bone resorption (RatLaps; type I collagen cross-links, bone formation (osteocalcin) and cartilage destruction (cartilage oligomeric matrix protein), and for the evaluation of antigen-specific and innate immune responsiveness. Ovariectomized mice displayed more severe arthritis than sham-operated controls. At termination of the experiment, arthritic control mice and non-arthritic ovariectomized mice displayed trabecular bone losses of 26% and 22%, respectively. Ovariectomized mice with arthritis had as much as 58% decrease in trabecular BMD. Interestingly, cortical BMD was decreased by arthritis but was not affected by hormonal status. In addition, markers of bone resorption and cartilage destruction were increased in arthritic mice, whereas markers of bone formation were increased in ovariectomized mice. This study demonstrates that the loss of endogenous estrogen and inflammation contribute additively and equally to osteoporosis in experimental postmenopausal polyarthritis. Markers of bone remodeling and bone marrow lymphocyte phenotypes indicate different mechanisms for the development of osteoporosis caused by ovariectomy and arthritis in this model. | |
| 16960951 | Does everybody need a team? | 2006 Sep | Multidisciplinary team care, defined as care provided by a group of health professionals from various disciplines, has been widely used in arthritis management since the 1950s. Its effectiveness in comparison with regular outpatient care has mainly been established in patients with rheumatoid arthritis (RA). Recent studies have shown that similar outcomes can be achieved in patients with RA at lower costs using care provided by a clinical nurse specialist. These latter findings suggest that the active components of the multidisciplinary team care model may not be related to the number or professional backgrounds of the health professionals involved, nor with their physical proximity, but rather to the provider's skills in rheumatology and the coordination of services. Because many patients with arthritis have healthcare needs that are not met through treatment by the rheumatologist alone and since traditional multidisciplinary team care in many countries is unavailable or may be undesirable in specific situations, the development and evaluation of alternative, comprehensive models of care delivery is recommended. | |
| 16265704 | Increased monocyte chemoattractant protein-1 in knee joints of rats with adjuvant-induced | 2005 Nov | OBJECTIVE: Imbalance of inflammatory and antiinflammatory cytokines plays a critical role in the pathogenesis of rheumatoid arthritis (RA). Precise determination of these cytokines would lead to better understanding of the progression of RA. METHODS: We developed an in vivo microdialysis technique to directly monitor cytokine profiles in knee joints of rats with adjuvant-induced arthritis (AIA). Microdialysates drained from knee joints of rats with AIA and controls were collected and cytokine concentrations were measured by ELISA. Pathological changes of the knee joints and the source of monocyte chemoattractant factor-1 (MCP-1) secretion were also determined by histology and immunohistochemistry. RESULTS: MCP-1 expression in knee joints was significantly higher in AIA rats with erosive changes in their ankles than in normal rats, while interleukin 6 (IL-6) levels were similar in both cases. IL-1beta and interferon-gamma were not detectable in the microdialysates. Increased synovial proliferation and mononuclear inflammatory infiltrates were observed. Synovial cells and mononuclear inflammatory cells expressed both MCP-1 and its receptor, CCR2. CONCLUSION: Our results indicate that the in vivo microdialysis technique is capable of detecting cytokines in the knee joints of rats. Increased expression of MCP-1 and CCR2 in knee joints of AIA rats suggests a role for this cytokine in triggering the mechanisms involved in the pathogenesis of knee joint after ankle erosion. | |
| 15878203 | An essential role for CCL3 in the development of collagen antibody-induced arthritis. | 2005 Sep 15 | CCL3 is a C-C family chemokine detected at high levels in the synovial tissue and fluids of rheumatoid arthritis (RA) patients. CCL3 binds to the chemokine receptors CCR1 and CCR5, which are expressed by inflammatory leukocytes such as macrophages and T cells present in the affected joints of RA patients. The present study was undertaken to investigate whether absence of CCL3 prevented development of inflammation and joint destruction in anti-type II collagen monoclonal antibody (anti-CII mAb)-induced arthritis. "CCL3 null mice were different from wild-type control mice in terms of body weight loss". In addition, CCL3 null mice exhibited milder clinical and histopathological scores following administration of anti-CII mAb and endotoxin. Moreover, the release of TNF in response to systemic administration of endotoxin was not affected in CCL3 null mice compared to wild-type mice, indicating that the phenotype was not attributable to a defect in endotoxin response. These results indicate that CCL3 plays an essential role in the development of inflammation and joint destruction induced by anti-CII mAb. |
