Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Flare-up reactions were induced in the rat chronic antigen-induced arthritis model (AIA), similar to those in mice and rabbits. After two consecutive immunizations (500 micrograms each, Day -21 and -14) with methylated bovine serum albumin (mBSA) in complete Freund's adjuvant (CFA), a biphasic primary arthritis was induced on Day 0 by intra-articular (i.a.) injection of 100 micrograms mBSA. The acute arthritic phase lasted 1 week, followed by chronic, mild joint swelling. Flare-up could then be induced on Day 40 by a second i.a. injection of 10-100 micrograms mBSA into the knee, with maximal flare-up reaction 2 days following the i.a. injection, and a return to chronic levels within 2 weeks. On Day 6 after induction of the flare-up, the inflamed joint showed massive cartilage and bone destruction; high numbers of alpha beta-T-cell-receptor-positive cells and macrophages, but only a few IL-2-receptor-carrying cells were detected in the inflamed synovial membrane. Induction of a second flare-up, 40 days after the first one, was possible by i.a. injection of 100 micrograms mBSA. Unlike in the mouse model, intravenous injection of up to 10 mg mBSA failed to induce flare-ups in the chronically inflamed joint.
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PMID:Induction of flare-up reactions in rat antigen-induced arthritis. 773 37

The objective of this study was to examine the effect of the stimulation of the immune system with Mycoplasma arthritidis superantigen (MAS) on joint inflammation and cartilage destruction. MAS was administered either alone or combined with a model of degenerative arthritis induced by intraarticular injection of collagenase enzyme. Intraperitoneal injection of MAS resulted in activation of peripheral lymphocytes in BALB/c mice, as shown by a proliferative response of splenocytes isolated from MAS-treated animals to IL-2-containing supernatant. Intraperitoneal or intra-articular administration of MAS alone at concentrations maximally activating lymphocytes had no detectable effect on joints. Intra-articular injection of collagenase resulted in some infiltration of inflammatory cells into the joints, hyperplasia and hypertrophy of synovial lining, pannus formation and surface loss of proteoglycans 7 days following the injection. At 21 days, the animals showed almost total loss of cartilage and minimal or no inflammation. Animals receiving MAS in addition to collagenase treatment showed similar changes in the joints. These data have demonstrated that activation of the immune system with MAS in vivo does not increase joint inflammation or cartilage degradation in enzymatically induced arthritis.
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PMID:Effect of Mycoplasma arthritidis superantigen on enzymatically induced arthritis in mice. 788 56

Proteoglycan (aggrecan)-induced arthritis is an autoimmune inflammatory animal model produced in genetically susceptible BALB/c mice. This animal model shows many similarities to human rheumatoid arthritis as indicated by clinical assessments, histopathological studies, and immunological parameters. The systemic immunization of mice with a select group of cartilage proteoglycans provokes immune responses to the immunizing antigen and then the production of cross-reactive antibodies to self proteoglycans. This is followed by an explosive proliferation of autoreactive T cells, especially in joint draining lymph nodes, accompanied by local (joint) inflammatory events. In the current experiments we found that lymphocytes from arthritic, or potentially arthritic but yet clinically asymptomatic animals, produced more IL-2 than those T cells obtained from animals immunized with nonarthritogenic PGs. In addition, synoviocytes isolated from prearthritic or arthritic animals produced several-fold more interleukin-1 beta (IL-1 beta) than cells from normal animals. Flow cytometric analysis indicated an autoantigen (mouse PG)-specific selective proliferation of surface Ig+/CD45R+ cells in prearthritic stages followed by the proliferation of predominantly T helper (CD4+) cells during and after the development of arthritis.
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PMID:Mediators and autopathogenic effector cells in proteoglycan-induced arthritic and clinically asymptomatic BALB/c mice. 792 85

The effects of the T-cell-directed immunosuppressant cyclosporin A (CsA) on the development of antigen-induced arthritis (AIA) in rats as well as on cytokine levels in synovial fluid and serum were determined. The treatment with CsA effectively inhibited the chronic phase of arthritis as demonstrated by decreased joint swelling and reduced histological arthritic score. In animals with AIA the level of IL-6 in the synovial fluid and serum is increased, showing good correlation with the severity of the disease. The CsA treatment reduced IL-6 levels to normal. IL-1, IL-2 and TNF-alpha do not seem to be directly involved in the pathogenic mechanisms of chronic arthritis.
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PMID:Influence of cyclosporin A on cytokine levels in synovial fluid and serum of rats with antigen-induced arthritis. 807 31

Collagen-induced arthritis is an arthritic disease that can be induced in rodents and primates. It is used widely as a model of disease processes and potential therapies. The immunology of collagen arthritis has some compelling parallels with human disease and these have been exploited recently in several novel ways to analyse the nature of autoreactivity against joint antigens and to test new therapies. Antibodies against lymphocyte surface markers, such as CD4, CD40L and MHC Class II, have been shown to suppress disease progression. Manipulation of cytokines, notably TNF-alpha, IL-1 and IL-2, has been extensively studied using the cytokines themselves, antibodies against cytokines and other antagonists with varied, but promising results. The search for antigen-specific immunosuppression has gained new impetus through manipulation of collagen arthritis by mucosal delivery of collagen to induce tolerance that suppresses disease. This review examines the salient features of collagen arthritis that are relevant to human disease and discusses the meaning and potential application of experimental therapies to the control of human arthritis.
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PMID:Collagen arthritis--what can it teach us? 808 63

Autoimmune diseases can be characterized by increases in Th cell activities, suggesting that inhibition of Th cell function might ameliorate autoimmunity. We have recently reported that administration of nonmitogenic anti-CD3 mAb (nmCD3) to nonautoimmune mice can induce long-term Th cell hyporesponsiveness, reflected by reduced IL-2 secretion upon re-exposure to Ag. This study was designed to determine the effects of nmCD3 on autoimmunity by using the murine collagen-induced arthritis model. Treatment of DBA/1 mice with nmCD3 delayed the onset and reduced the severity of arthritis in mice immunized with type II collagen (CII). This effect was not caused by depletion of T cells or modulation of TCR. The observed inhibition of arthritis was not caused by decreased Ab production, as anti-CII titers were not affected. Rather, lymph node cells from CII-immunized mice treated with nmCD3 were hyporesponsive to in vitro stimulation with CII. This hyporesponsiveness was reflected by a marked decrease in secretion of IL-2 and IFN-gamma, but not of IL-4, which suggests that nmCD3 had its principal effect on Th1 cells. The hyporesponsiveness was not Ag-specific, because IL-2 and IFN-gamma production in response to a pan-T cell mitogen was also reduced. These results demonstrate that induction of Th1 cell hyporesponsiveness with nmCD3 can significantly alter the course of CIA and suggest that IL-2 and/or IFN-gamma play a crucial role in disease pathogenesis.
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PMID:Induction of T helper cell hyporesponsiveness in an experimental model of autoimmunity by using nonmitogenic anti-CD3 monoclonal antibody. 808 1

Cytofluorometric analysis was performed to characterize the immunophenotype of lymphocytes of the synovial fluid (SF) and the peripheral blood (PB) from patients suffering from juvenile chronic arthritis (JCA) or rheumatoid arthritis (RA). The most obvious difference could be found in expression of the surface protease aminopeptidase N (AP N/CD13). Whereas monoclonal antibodies specific to CD13 failed to reveal surface expression on lymphocytes of the PB; 63 +/- 15% of SF T cells gave positive staining for CD13 using Leu-M7. No correlation between CD13 expression and joint disease could be found in patients who had different types of inflammatory joint effusions. CD13 expression of T cells was also found in synovial tissue and inflammatory serous cavity effusions. Fixation of T cells revealed the presence of intracellular CD13 antigen already located in the PB T cells of healthy individuals. Induction of CD13 expression on PB T cells could be demonstrated after incubation with Con A/IL-2 or SF from patients with RA. Our findings suggest a role for AP N as a new activation-associated molecule of T lymphocytes.
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PMID:Demonstration of CD13/aminopeptidase N on synovial fluid T cells from patients with different forms of joint effusions. 809 41

The induction of tolerance, particularly by intervention before established immunity, is widely accepted. We studied the effects of intravenous (i.v.) administration of hen egg lysozyme (HEL), before as well as after immunization, on a HEL-induced arthritis. Arthritis and also cartilage destruction were almost completely suppressed when 100 micrograms HEL was injected before immunization. Antigen-specific proliferative T cell responses and IL-2 production in vitro were inhibited. Antigen-specific immunoglobulin and IgG1 titres were equal in control and tolerized mice, in contrast to lowered IgG2a titres in tolerized animals. Detailed histological studies showed that the immune complex-dependent polymorphonuclear cell phase (< 24 h after arthritis induction) was equal for control and HEL-injected mice. Only in the T cell-dependent phase of the arthritis (> 24 h), did suppression become pronounced in tolerized mice. I.v. administration of 100 micrograms HEL after immunization could only marginally reduce infiltrate and exudate, and no reduction of cartilage destruction was seen. An elegant way to interfere in an established immunity can be offered by creation of bystander suppression. We show that i.v. administration of HEL followed by triggering with HEL, at the moment either of immunization or of arthritis induction, does not reduce a methylated bovine serum albumin (BSA)-arthritis. We conclude that arthritis can be suppressed almost totally when HEL is injected intravenously before immunization. Treatment after immunization is less effective. The i.v. induced suppression is T cell-mediated and and antigen-specific: no bystander suppression circuit can be generated.
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PMID:Suppression of hen egg lysozyme-induced arthritis by intravenous antigen administration: no role in this for antigen-driven bystander suppression. 814 64

Reactive arthritis (ReA) is a sterile inflammatory arthritis which usually occurs after an enteric or genitourinary infection. In recent years it has been recognized that synovial fluid mononuclear cells from an affected joint demonstrate marked proliferative responses if incubated with preparations of the organism triggering the arthritis; peripheral blood mononuclear cell (PBMC) responses are typically much smaller. One interpretation of this finding is that recognition of the triggering organism is enhanced within the joint compared to peripheral blood, but it could also be argued that the PBMC responses are actually depressed during acute arthritis. We have examined this possibility in a longitudinal study of PBMC proliferative responses in patients with ReA. In this study we have demonstrated that PBMC proliferative responses to the triggering organism were indeed depressed during acute ReA, and showed a significant increase after recovery from the arthritis. These findings also applied to PBMC recognition of the recall antigen PPD, and to the response to IL-2.
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PMID:A longitudinal study of peripheral blood mononuclear cell proliferative responses to bacterial antigens in reactive arthritis. 815 82

The angiogenesis inhibitor AGM-1470 has recently been reported to inhibit collagen-induced arthritis in rats. To determine if the anti-arthritic effects of AGM-1470 might be due to T cell inhibition, we have studied its effects on T cell responses in vitro. Responses of human cells to tetanus toxoid (TT), and those of murine splenocytes to staphylococcal enterotoxin (SE), mitogens or a mls difference were inhibited by AGM-1470. Responses of human cells to SE, OKT3 and PHA were all partially inhibited on day 2 (d2) but not d3, and in fact were augmented on d6-8. The amount of IL-2 in SEA cultures was augmented on d4 and d5. There were no differences in the expression of CD3, CD4, CD8, CD25, CD45RA, CD45RO, LFA-1, VLA-4 or VLA-6 in inhibited cultures, except for slight decreases in CD25 and CD45RO in TT cultures. These results indicated that the angiogenesis inhibitor AGM-1470 also modulates human and murine lymphocyte function.
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PMID:Modulation of T lymphocyte function by the angiogenesis inhibitor AGM-1470. 827 96


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