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ID PMID Title PublicationDate abstract
10914696 Use of COX-2 specific inhibitors in operative and nonoperative management of patients with 2000 Jul Arthritis is a major burden on society and the individual. Arthritis affects all age groups and races, and is more prevalent in women than men by approximately 1.65:1. Nearly one half of people aged > or = 65 years report the presence of arthritic symptoms; however, by no means is arthritis a disease of only the elderly. The burden of arthritis will continue to increase due to expected future increases in the size and age of the general population. Currently, the total costs of medical care and lost wages due to arthritis are in excess of 64 billion dollars per year in the United States. For the individual, arthritis may cause substantial pain, impair mobility, curtail physical activity, and have a negative impact on mental health. The two most common forms of arthritis, osteoarthritis and rheumatoid arthritis, have major health complications. From the perspective of the orthopedic surgeon, the aim of treatment of arthritic conditions includes early, accurate diagnosis and appropriate treatment to minimize pain and maximize function. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used as part of the medical management of patients with arthritis. These medications are effective in mitigating pain and inflammation associated with arthritis. However, side effects (most notably of the gastrointestinal tract) have limited the more widespread use of NSAIDs. The newer cyclooxygenase-2 (COX-2) inhibitors have proven to be efficacious and have demonstrated fewer gastrointestinal adverse effects. Furthermore, COX-2 inhibitors do not appear to adversely affect platelet function. For these reasons, consideration may be given to using COX-2 perioperatively, however, drug interactions must be closely monitored.
11708423 Use of a peptide based enzyme immunoassay in diagnosis of Chlamydia trachomatis triggered 2001 Nov OBJECTIVE: To assess the presence of circulating IgA and IgG antibodies to Chlamydia trachomatis in sera of patients with reactive arthritis (ReA) and other arthritides. METHODS: A peptide based enzyme immunoassay (EIA) was used to study 132 patients divided into 5 groups: C. trachomatis triggered ReA, uroarthritis, enteroarthritis, oligoarthritis, and rheumatoid arthritis (RA). Followup sera were available from 19 patients. RESULTS: An increased prevalence of C. trachomatis antibodies was observed in patients with ReA triggered by C. trachomatis; 18/23 (78%) had IgA and 19/23 (83%) had IgG antibodies. In patient groups with uroarthritis (n = 12), enteroarthritis (n = 56), oligoarthritis (n = 16), and RA (n = 25), C. trachomatis IgA/IgG antibodies were detected in 58%/75%, 27%/21%, 25%/31%, and 20%/32% of patients, respectively. Both the IgA and IgG antibodies were positive in 74%, 50%, 16%, 25%, and 12% of the patients with C. trachomatis triggered ReA, uroarthritis, enteroarthritis, oligoarthritis, and RA, respectively. Based on positivity of both isotypes the sensitivity of the assay was 74% and specificity 84%. In the followup sera, an association between circulating C. trachomatis-specific antibody concentrations and clinical disease outcome of the arthritis was seen in patients with culture-positive C. trachomatis triggered ReA. CONCLUSION: C. trachomatis species-specific peptide EIA correlates well with conventional diagnosis of primary C. trachomatis infection in patients with ReA. This assay may be a valuable contribution to the diagnosis of C. trachomatis triggered ReA.
9091584 An HLA-DR1 transgene confers susceptibility to collagen-induced arthritis elicited with hu 1997 Mar 17 Rheumatoid arthritis (RA) is an autoimmune disease that is strongly associated with the expression of several HLA-DR haplotypes, including DR1 (DRB1*0101). Although the antigen that initiates RA remains elusive, it has been shown that many patients have autoimmunity directed to type II collagen (CII). To test the hypothesis that HLA-DR1 is capable of mediating an immune response to CII, we have generated transgenic mice expressing chimeric (human/mouse) HLA-DR1. When the DR1 transgenic mice were immunized with human CII (hCII), they developed a severe autoimmune arthritis, evidenced by severe swelling and erythema of the limbs and marked inflammation and erosion of articular joints. The development of the autoimmune arthritis was accompanied by strong DR1-restricted T and B cell responses to hCII. The T cell response was focused on a dominant determinant contained within CII(259-273) from which an eight amino acid core was defined. The B cell response was characterized by high titers of antibody specific for hCII, and a high degree of cross-reactivity with murine type II collagen. These data demonstrate that HLA-DR1 is capable of presenting peptides derived from hCII, and suggest that this DR1 transgenic model will be useful in the development of DR1-specific therapies for RA.
10419604 Denaturation of type II collagen in articular cartilage in experimental murine arthritis. 1999 Jul Degradation of type II collagen is thought to be a key step in the destruction of articular cartilage in patients with rheumatoid arthritis or osteoarthritis. The aim of this study was to investigate whether type II collagen degradation is associated with cartilage destruction. Type II collagen degradation was studied in two murine arthritis models, zymosan-induced arthritis (ZIA), which develops reversible articular cartilage damage based on proteoglycan analysis, and antigen-induced arthritis (AIA), in which there is irreversible damage to the cartilage. Type II collagen degradation was assayed immunohistochemically using the COL2-3/4m antibody which recognizes denatured type II collagen, such as is produced by collagenase cleavage. In both models, degradation of type II collagen was observed in the non-calcified articular cartilage of arthritic but not of control knees. In the patella-femoral compartment, collagen denaturation started to increase on day 3 (ZIA) and day 7 (AIA) and remained high on day 14. In contrast, in the tibia-femoral compartment, type II collagen breakdown was not increased before 14 days in either model. By 28 days, collagen denaturation was strongly reduced in the patella-femoral compartment in the ZIA model, but persisted in the tibia-femoral compartment in both models. In conclusion, increased type II collagen degradation was found in articular cartilage of both ZIA and AIA animals. Since ZIA does not develop irreversible cartilage destruction, this indicates that cartilage may have the ability to withstand a limited degree of type II collagen degradation without developing irreversible damage.
9780220 Localization of quantitative trait loci regulating adjuvant-induced arthritis in rats: evi 1998 Oct 15 Adjuvant-induced arthritis (AIA) in rats is a widely used autoimmune experimental model with many features similar to rheumatoid arthritis (RA). To identify potential genetic regulatory mechanisms in RA, we conducted genome-wide linkage analysis in F2 progeny of arthritis-susceptible Dark Agouti (DA) and relatively resistant Fischer 344 (F344) inbred rats. We compared the data with our previously reported investigation of collagen-induced arthritis (CIA), which was expanded in the follow-up study reported in this work. We found two quantitative trait loci (QTLs) in common, i.e., Aia1/Cia1 on chromosome 20, which includes the MHC, and Aia3/Cia3 on chromosome 4. We also identified a second unique QTL in AIA, Aia2, on chromosome 4. Interestingly, the QTL region on chromosome 4 (Aia3/Cia3), like the MHC, appears to be involved in several other autoimmune diseases in rats, including insulin-dependent diabetes, thyroiditis, and experimental autoimmune uveitis. Moreover, an analysis of conserved synteny among rats, mice, and humans suggested that Aia2 and Aia3/Cia3, like Aia1/Cia1, contain candidate genes for several autoimmune/inflammatory diseases in mice and humans, including diabetes, systemic lupus erythematosus, inflammatory bowel disease, asthma/atopy, multiple sclerosis, and RA. The rat models appear to provide a powerful complementary approach to identify and characterize candidate genes that may contribute to autoimmune diseases in several species.
10224865 [Psoriatic arthritis--diagnostic criteria]. 1998 Arthritis psoriatica has been known for over 160 years, however, not long ago it became a separate nosologic unit. In 1964 American Rheumatological Society introduced the name arthritis psoriatica, which is obligatory nowadays. It was thought in the beginning that the inflammation may coexist with psoriasis accidentally only, whereas epidemiological studies, clinical observations and serologic data excluded such a simple relation. Since the international diagnostic criteria were established and also the rheumatoid factor was discovered it has been clear there's a direct relation between arthritis psoriatica and dermatologic changes of a psoriasis type. Therefore it is a disease where rheumatology and dermatology meet with each other. The aim of our study was to collect the knowledge about the diagnosis of arthritis psoriatica.
9777960 Induction of arthritis in BALB/c mice by cartilage link protein: involvement of distinct r 1998 Oct Both type II collagen and the proteoglycan aggrecan are capable of inducing an erosive inflammatory polyarthritis in mice. In this study we provide the first demonstration that link protein (LP), purified from bovine cartilage, can produce a persistent, erosive, inflammatory polyarthritis when injected repeatedly intraperitoneally into BALB/c mice. We discovered a single T-cell epitope, located within residues 266 to 290 of bovine LP (NDGAQIAKVGQIFAAWKLLGYDRCD), which is recognized by bovine LP-specific T lymphocytes. We also identified three immunogenic regions in bovine LP that contain epitopes recognized by antibodies in hyperimmunized sera. One of these B-cell regions is found in the most species-variable domain of LP (residues 1 to 36), whereas the other epitopes are located in the most conserved regions (residues 186 to 230 and 286 to 310). The latter two regions contain an AGWLSDGSVQYP motif shared by the G1 globulin domain of aggrecan core protein, versican, neurocan, glial hyaluronan-binding protein, and the hyaluronan receptor CD44. Our data reveal that the induction of arthritis is associated with antibody reactivities to B-cell epitopes located at residues 1 to 19. Together, these observations show that another cartilage protein, LP, like type II collagen and the proteoglycan aggrecan, is capable of inducing an erosive inflammatory arthritis in mice and that the immunity to LP involves recognition of both T- and B-cell epitopes. This immunity may be of importance in the pathogenesis of inflammatory joint diseases, such as juvenile rheumatoid arthritis, in which cellular immunity to LP has been demonstrated.
10843707 Combined effects of IL-12 and IL-18 on the induction of collagen-induced arthritis. 2000 Jun 15 IL-18 expression has recently been detected in rheumatoid arthritis (RA) synovial membrane. We investigated the mechanisms by which IL-18-induced collagen-induced arthritis in DBA/1 mice primed intradermally with type II bovine collagen in IFA and boosted i.p. 21 days later with CII in saline. Mice were injected i.p. with rIL-12, rIL-18, or both (100 ng) during days -1 to 4 and again on days 20-24. Control mice received PBS. Mice treated with IL-12 or IL-18 alone developed significantly higher incidence and more severe disease compared with controls. These were elevated further by combination treatment with IL-12 and IL-18. The cytokine treatments led to markedly enhanced synovial hyperplasia, cellular infiltration, and cartilage erosion compared with controls. Cytokine-treated mice produced significantly more IFN-gamma, TNF-alpha, and IL-6 than the controls. Interestingly, IL-18-treated mice produced more TNF-alpha and IL-6, but less IFN-gamma, compared with mice treated with IL-12. Furthermore, splenic macrophages from DBA/1 mice cultured in vitro with IL-18, but not IL-12, produced substantial amounts of TNF-alpha. Mice treated with IL-18 or IL-18 plus IL-12 produced markedly more IgG1 and IgG2a anti-collagen Ab compared with controls, whereas IL-12 treatment only led to an enhanced IgG2a response. Together these results demonstrate that IL-18 can promote collagen-induced inflammatory arthritis through mechanisms that may be distinct from those induced by IL-12.
10884526 Anti-inflammatory and analgesic effects of the phosphodiesterase 4 inhibitor rolipram in a 2000 Jul 7 There has been much interest in strategies which modulate tumour necrosis factor-alpha (TNF-alpha) levels and/or function in rheumatoid arthritis. The elevation of intracellular levels of cyclic AMP in leukocytes by phosphodiesterase 4 inhibitors is accompanied by significant inhibition of the production of TNF-alpha. Nevertheless, these drugs may enhance the hyperalgesia induced by a range of inflammatory mediators, including TNF-alpha. In the present study, we examined the effects of the phosphodiesterase 4 inhibitor rolipram on the local inflammatory infiltrate and hyperalgesia in a rat model of adjuvant-induced arthritis. Rolipram (3 mg/kg) was administered by oral gavage from day 10 to 14 after disease induction. Pretreatment with rolipram abrogated oedema formation and significantly inhibited hyperalgesia. Histopathological analysis revealed a marked inhibition of cellular influx as well as bone and cartilage destruction. Serum and local TNF-alpha levels were suppressed in treated animals whereas there were little changes in interleukin-1beta levels. Although cyclic AMP elevating agents may affect nociceptor threshold to increase the hyperalgesic responses acutely, they also possess significant anti-inflammatory activity, which may hinder local mediator release and/or action. The anti-inflammatory effects of rolipram predominate during this chronic arthritis model in the rat.
9259407 New nortriterpenoid isolated from anti-rheumatoid arthritic plant, Tripterygium wilfordii, 1997 Aug 7 Preparations of Tripterygium wilfordii, "Thunder God vine", have been used in China to treat rheumatoid arthritis. Rheumatoid arthritis, as well as solid tumors, is closely associated with neovascularization. Antiarthritic drugs therefore may modulate tumor growth as well as neovascularization. We found that a compound purified from T. wilfordii, the nortriterpenoid, demethylzeylasteral (TZ-93), inhibited the proliferation of vascular endothelial cells approximately 30 times more effectively than it did for the proliferation of human tumor cells. In in vitro assays using bovine aortic endothelial cells, TZ-93 at non-toxic doses inhibited cell migration, expression of urokinase-type plasminogen activator (uPA) mRNA and uPA activity. Exogenous addition of uPA restored the inhibitory effect of TZ-93 on cell migration. In dorsal air-sac assays in BALB/c mice, the oral administration of 3 mg/kg/day TZ-93 for 5 days partially inhibited, and 30 mg/kg/day almost completely abrogated, the development of capillary networks induced by human hepatoblastoma cells. Similarly, 0.3 mg/kg/day TZ-93 partially inhibited, and 3 or 30 mg/kg/day almost completely blocked, the growth of mouse B16-F10 melanoma cells in a tumor implantation assay. The highest dose of TZ-93 significantly reduced the growth of well-vascularized tumors with volumes of more than 500 mm3. TZ-93 treatment of tumor-bearing mice significantly decreased the density of microvessels in the tumors. We conclude that TZ-93 may be useful in treating highly vascularized and metastatic tumors as well as other angiogenic diseases.
9281381 Epidemiology and estimated population burden of selected autoimmune diseases in the United 1997 Sep Autoimmune diseases cause significant and chronic morbidity and disability. The actual number of persons in the United States that are affected by autoimmune diseases and the resultant magnitude of their impact on the public's health are limited to a few specific diseases. In order to understand the clinical, public health and economic importance of these diseases it is necessary to have estimates of incidence and prevalence rates in the population. In this analysis, we estimate the number of persons affected by 24 autoimmune diseases in the United States by applying mean weighted prevalence and incidence rates obtained from published articles to U. S. Census data. The study was restricted to 24 autoimmune predefined diseases for which there was direct or indirect evidence for autoimmune pathogenesis. Subsequently, we used computerized search software and ancestry searching (bibliographies) to conduct a comprehensive search of articles published from 1965 to the present. Eligible studies included those which adhered to standard disease definitions and which included population-based estimates of incidence or prevalence rates. Mean weighted incidence and prevalence rates were calculated from eligible published studies with greater weight proportionately given to larger studies. The mean rates were then applied to the U.S. Census population figures to estimate the number of persons currently afflicted with each disease and the number of new cases occurring each year in the United States. Only U.S. and European studies were used to estimate prevalence and incidence rates when there were at least six eligible studies available for a disease. When there were fewer than six studies, all available studies were included, regardless of country of origin. The number of eligible incidence and prevalence studies found in the literature varied considerably between the 24 autoimmune diseases selected. The largest number of eligible prevalence studies were conducted on multiple sclerosis (MS), rheumatoid arthritis, and systemic lupus erythematosus (SLE) (>/=23), followed by insulin-dependent diabetes (IDDM), myasthenia gravis, primary biliary cirrhosis, and scleroderma (>/=7). There were only one to four eligible studies done on 11 other diseases, and no prevalence studies on 6 diseases. Incidence studies were less frequent but the largest number of studies were conducted on IDDM (n = 37) and MS (n = 28), followed by Graves' disease/hyperthyroidism, glomerulonephritis, primary biliary cirrhosis, rheumatic fever, rheumatoid arthritis, scleroderma, and SLE (>/=9). On the other 11 diseases, there were one to six eligible studies, and no studies on 5 diseases. There were no eligible incidence or prevalence studies on Goodpasture's syndrome, idiopathic thrombocytopenia purpura, or relapsing polychondritis. Overall we estimate that 8,511,845 persons in the United States or approximately 1 in 31 Americans are currently afflicted with one of these autoimmune diseases. The diseases with the highest prevalence rates were Graves'/hyperthyroidism, IDDM, pernicious anemia, rheumatoid arthritis, thyroiditis, and vitiligo, comprising an estimated 7,939, 280 people or 93% of the total number estimated. Glomerulonephritis, MS, and SLE added an estimated 323,232 people. The prevalence of the other diseases reviewed were rare, less than 5.14/100,000. Most diseases were more common in women. From the incidence data we estimate that 237,203 Americans will develop an autoimmune disease in 1996 and that approximately 1,186,015 new cases of these autoimmune diseases occur in the United States every 5 years. Women were at 2.7 times greater risk than men to acquire an autoimmune disease. After reviewing the medical literature for incidence and prevalence rates of 24 autoimmune diseases, we conclude that many autoimmune diseases are infrequently studied by epidemiologists. As a result the total burden of disease may be an underestimate. (ABSTRACT TRUNCATED)
9542779 TNF-alpha induces the transcription factor Egr-1, pro-inflammatory cytokines and cell prol 1998 In rheumatoid arthritis (RA) cell proliferation and altered metalloproteinase expression of synovial lining cells are associated with increased levels of TNF-alpha in the rheumatoid joint. We previously showed that synoviocytes of RA patients express high levels of the transcription factor Egr-1. Here we report that TNF-alpha is capable of inducing high Egr-1 mRNA levels in human skin fibroblasts and in synoviocytes from both, RA and reactive arthritis patients. Moreover, we observed in vitro a marked increase in fibroblast proliferation, a loss of growth inhibition by cell-to-cell contact with pannus-like cell growth and an altered cytokine expression pattern when synoviocytes were cultured in presence of TNF-alpha.
10725428 Integrity and full coding sequence of B19 virus DNA persisting in human synovial tissue. 2000 Apr Primary infection by human parvovirus B19 is often accompanied by arthropathy of varying duration, of which the most severe cases can be indistinguishable from rheumatoid arthritis (RA). While this might seem to imply a role in RA pathogenesis, recent studies have verified long-term persistence of B19 DNA in synovial tissue not only in patients with rheumatoid or juvenile arthritis, but also in immunocompetent, non-arthritic individuals with a history of prior B19 infection. However, the latter data are based on PCR amplification of short segments of DNA, with little sequence information. We determined the nucleotide sequence and examined the integrity of the protein-coding regions of B19 genomes persisting in synovial tissue and compared the results with data from synovial tissues of recently infected patients. In synovium of both previously and recently infected subjects, the viral coding regions were found to be present in an apparently continuous, intact DNA molecule. Comparison with sequences reported from blood or bone marrow showed that the synoviotropism or persistence of the B19 virus DNA was not due to exceptional mutations or particular genotype variants. The synovial retention of full-length viral genomes may represent a physiological process functioning in long-term storage of foreign macromolecules in this tissue.
10436972 [Inclusion body myositis: clinical and myopathological features]. 1997 Sep Inclusion body myositis has been recognized as a major form of idiopathic inflammatory myopathy. An old male patient with insidious onset and slowly progressive muscular weakness and artrophy has been reported in this article. The duration of symptom before biopsy was 23 years. The first symptom was dysphagia, and muscular weakness developed seven years later. Muscular atrophy was predominant symmetrically and proximally, particularly the quadriceps femoris muscles. Cervical and abdominal muscles were also affected. Myalgia was absent. Electromyogrophy showed myopathic alterations. Erythrocyte sedimentation rate, creatine kinase, immunoglobulins G increased slightly or moderately. Rheumatoid factor was positive, and he had been diagnosed as having rheumatoid arthritis for 23 years. Inclusion body myositis was ultimately diagnosed based on the muscle biopsy which showed mononuclear cell invasion of nonnecrotic muscle fibers, the characteristic rimmed vacuoles in cryostat sections and cytoplasmic inclusion bodies consisted of plenty of tubulofilaments by electron microscope.
11441109 IL-1-independent role of IL-17 in synovial inflammation and joint destruction during colla 2001 Jul 15 T cell IL-17 displays proinflammatory properties and is expressed in the synovium of patients with rheumatoid arthritis. Its contribution to the arthritic process has not been identified. Here, we show that blocking of endogenous IL-17 in the autoimmune collagen-induced arthritis model results in suppression of arthritis. Also, joint damage was significantly reduced. In contrast, overexpression of IL-17 enhanced collagen arthritis. Moreover, adenoviral IL-17 injected in the knee joint of type II collagen-immunized mice accelerated the onset and aggravated the synovial inflammation at the site. Radiographic and histologic analysis showed markedly increased joint destruction. Elevated levels of IL-1beta protein were found in synovial tissue. Intriguingly, blocking of IL-1alphabeta with neutralizing Abs had no effect on the IL-17-induced inflammation and joint damage in the knee joint, implying an IL-1 independent pathway. This direct potency of IL-17 was underscored in the unabated IL-17-induced exaggeration of bacterial cell wall-induced arthritis in IL-1beta(-/-) mice. In conclusion, this data shows that IL-17 contributes to joint destruction and identifies an IL-1-independent role of IL-17. These findings suggest IL-17 to be a novel target for the treatment of destructive arthritis and may have implications for tissue destruction in other autoimmune diseases.
11803744 [Atlanto-axial kyphosis]. 2001 Dec Atlantoaxial kyphosis (AAK) is a rare sagittal deformity of the occiptoatlantoaxial junction. It is defined as a subgroup of anterior translatory atlantoaxial instability. AAK is a symptom of several ligamentours or bony disorders of the craniocervical junction; however, rheumatoid arthritis and trauma are the most common causes for AAK. AAK can be diagnosed on lateral radiographic views of the upper cervical spine if the angle between McGregor's line and the atlas plane is less than-15 degrees or the atlas-axis angle is greater 105 degrees. Treatment modalities for AAK depend on the ability to reduce the deformity. If closed reduction is achieved, posterior atlantoaxial fusion by sublaminar wiring according to Brooks or transarticular screw fixation according to Magerl are possible choices. Irreducible AAK can be treated with a combined transoral decompression, anterior plating according to Harms, and posterior wiring according to Brooks. This staged therapy for AAK was successful in our rheumatoid patient population with AAK.
10446862 Delayed onset and reduced severity of collagen-induced arthritis in interleukin-6-deficien 1999 Aug OBJECTIVE: To investigate the roles of interleukin-6 (IL-6) in the pathogenesis of rheumatoid arthritis (RA) by studying its effect on murine collagen-induced arthritis (CIA). METHODS: IL-6-deficient (IL-6-/-) mice with a genetic background of susceptibility to CIA were generated by backcrossing them with DBA/1J mice for 8 generations. Clinical and immunologic features were compared between these mice and IL-6 wild-type (IL-6+/+) littermates with CIA. RESULTS: Serum IL-6 levels increased during the development of CIA in IL-6+/+ mice. Two prominent peaks were observed. The first was coincident with the onset of arthritis, and the second one was observed during exacerbation of the disease. The onset of arthritis in IL-6-/- mice was delayed for 2 weeks compared with that in IL-6+/+ mice, and the severity of arthritis, as indicated by the arthritis score, remained significantly lower in IL-6-/- mice during the entire followup period (14 weeks), although all IL-6-/- mice developed definite arthritis as did the IL-6+/+ mice. Histologic severity was also reduced in IL-6-/- mice. In addition, radiologic changes such as osteopenia and bone erosion were reduced significantly in these animals. Both humoral and cellular responses to type II collagen (CII) in IL-6-/- mice were reduced to about half those in IL-6+/+ mice. In addition, enhanced production of IL-4 and IL-10 in response to concanavalin A stimulation was observed in IL-6-/- mice. CONCLUSION: IL-6 plays an important role in the development of CIA, and both suppression of specific immune responses to CII and a tendency to a shift toward a Th2 cytokine profile might contribute in part to the attenuation of CIA in IL-6-/- mice. These findings suggest that blockade of IL-6 might be beneficial in the treatment of RA.
9920019 Amelioration of collagen-induced arthritis and suppression of interferon-gamma, interleuki 1999 Jan OBJECTIVE: To investigate the therapeutic effects and possible mechanisms of action of constitutive expression of interferon-beta (IFNbeta) by syngeneic fibroblasts from DBA/1 mice in the collagen-induced arthritis (CIA) model. METHODS: Immortalized embryonic DBA/1 fibroblasts were infected with a retrovirus expressing murine IFNbeta. IFNbeta-expressing fibroblasts were then implanted intraperitoneally into mice immunized with bovine type II collagen. The effect of IFNbeta on paw swelling, anticollagen antibody levels, IgG1/IgG2a isotype profiles, arthritis score, histologic joint damage, and cytokine secretion from lymph node cells and from bone marrow-derived macrophages was assessed. RESULTS: A single injection of IFNbeta-secreting fibroblasts was sufficient to prevent arthritis or to ameliorate existing disease. Thus, IFNbeta reduced the clinical score and paw swelling irrespective of whether the injection was administered before or after disease onset in treated mice, compared with that in the untreated control group (P < 0.05). Histologic findings in the IFNbeta-treated mice were markedly less severe than in the control group (P < 0.001). This effect was accompanied by a decrease in total anticollagen IgG levels, a decrease in anticollagen IgG2a, and an increase in IgG1. In vitro, supernatants from these engineered fibroblasts inhibited collagen-induced interferon-gamma secretion from lymph node cells, and reduced the levels of tumor necrosis factor alpha and interleukin-12 produced by lipopolysaccharide/IFNgamma-treated bone marrow-derived macrophages. This effect was specific, since it was reversed with anti-IFNbeta polyclonal antibodies. CONCLUSION: These results indicate that IFNbeta, which is currently used as a treatment for relapsing, remitting multiple sclerosis, is a potent immunomodulatory and antiinflammatory cytokine in CIA and should be considered for the treatment of rheumatoid arthritis.
19078390 Bronchiolitis obliterans with organizing pneumonia (BOOP) heralding anti-Jo-1-positive pol 1999 Aug We report a 51-year-old man who presented with 3 weeks of polyarthritis with fever, nonproductive cough, bibasilar crackles, tachypnea, and hypoxia. Initial laboratory data showed an increased erythrocyte sedimentation rate, rheumatoid factor, and anti-Jo-1 antibody. Imaging studies showed bilateral lower lobe infiltrates of the lung. A transbronchial biopsy specimen revealed characteristic findings for bronchiolitis obliterans organizing pneumonia (BOOP). About 6 months later, he developed profound proximal muscle weakness with a dramatic increase in creatine phosphokinase and aldolase and a further elevation of anti-Jo-1. Muscle biopsy specimen findings were consistent with polymyositis.This represents an unusual case in which BOOP occurred at the onset of an illness initially suggestive of rheumatoid arthritis (RA). The anti-Jo-1-positivity led to close follow up and later discovery of evolution into polymyositis. BOOP can be an early feature of polymyositis as well as RA.
9159533 Immunocytochemical analysis of tissue kallikrein and the kinin moiety in rheumatoid synovi 1997 Apr Polymorphonuclear leucocytes (PMNs) from the synovial fluid of patients with rheumatoid arthritis (RA) showed reduced tissue kallikrein and kinin immunoreactivity in comparison with blood PMNs from healthy individuals as judged visually using confocal microscopy. Similarly, synovial fluid PMNs exhibited reduced tissue kallikrein immunoreactivity as compared with blood PMNs from the same RA patients. Blood PMNs stimulated to degranulate in vitro also displayed less immunostaining for tissue kallikrein and kinin than non-stimulated PMNs. By contrast, no difference in kininogen immunostaining was detected between RA synovial fluid PMNs and blood PMNs from healthy people. It is considered that the results support the hypothesis that tissue kallikrein, released from the granules of RA synovial fluid PMNs, cleaves the kinin moiety from multifunctional kininogen protein on the surface of the PMNs.