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)

We investigated the immunoregulatory properties of a recently described inhibitor of lymphocyte proliferation, suppressin (SPN). It was determined that preincubation of murine leukocytes with SPN enhances natural killer cell (NK) activity. In addition, SPN potentiates interferon-gamma (IFN-gamma) augmentation of NK activity. Furthermore, preincubation of murine leukocytes with SPN induces the production of IFN-alpha/beta. The IFN-alpha/beta produced is active in NK assays as well as vesicular stomatitis virus neutralization assays. In vivo, SPN increases the time of survival of C57BL/6 mice injected with EL-4 lymphoma cells. Interestingly, SPN inhibits immunoglobulin (IgA, IgG, and IgM) production in response to the mitogen, concanavalin A in a dose-dependent manner. Collectively, the above data indicate SPN may have numerous applications in clinical science including tumor surveillance and autoimmune diseases such as arthritis.
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PMID:Immunomodulatory characteristics of a novel antiproliferative protein, suppressin. 212 98

This paper gives a short review on the function, pharmacokinetics, and therapeutic application of recombinant interferon-gamma (rIFN-gamma) in dermatology. Simultaneously, our own experiences are presented for 57 patients (phase II study) suffering from genital warts (21 patients), psoriatic arthritis (10 patients), psoriasis vulgaris (three patients), malignant melanoma (six patients), bowenoid papulosis (four patients), Behcet's disease (four patients), basal cell carcinoma (six patients), as well as herpes simplex recidivans, epidermodysplasia verruciformis, and mycosis fungoides (one patient each). We conclude that there might be an indication for treatment with rIFN-gamma in genital warts, bowenoid papulosis, Behcet's disease, and microbial infections, such as leprosy and cutaneous leishmaniasis. Even though there are reports of a limited beneficial effect of rIFN-gamma on arthritis and skin lesions in psoriasis, we failed to observe any in 10 patients. The main side effects in our low-dose study (50-100 micrograms/d) were mild fever (78%), fatigue (78%), and myalgia (65%). Laboratory tests revealed an increase in the serum triglyceride level, in particular, in psoriatic patients.
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PMID:Recombinant interferon-gamma (rIFN-gamma) in dermatology. 212 42

We evaluated the effect of 47 serum samples obtained from 34 children with juvenile chronic arthritis (JCA) on mitogen-induced proliferation of normal peripheral blood lymphocytes (nPBL). We found that sera from patients with active disease, and particularly those with the systemic form, inhibited significantly PHA-induced proliferation of nPBL at all the PHA concentrations tested. This inhibitory activity was independent of the treatment and was correlated with the value of the erythrocyte sedimentation rate. Part of the JCA sera inhibitory effect could be reversed by the addition of exogenous interleukin 2 (IL-2), but not of interleukin 1 (IL-1) or interferon-gamma, moreover, JCA sera were able to partially inhibit the IL-2 dependent proliferation of CTLL. When we tested serum fractions obtained by Sephadex G-200 chromatography for their inhibitory activity, we observed that: a) two major peaks of inhibitory activity on PHA-induced proliferation were present: peak 1 with MW less than 600,000 and peak 2 with MW between 70,000 and 35,000; b) the inhibitory activity present in the high MW peak was in part IL-2 related; and c) both peaks contained elevated levels of acute phase proteins (APP) which are known to inhibit mitogen-induced lymphocyte proliferation. We conclude that sera from patients with active systemic JCA contain inhibitory activity on mitogen-induced lymphocyte proliferation. We conclude that sera from patients with active systemic JCA contain inhibitory activity on mitogen-induced lymphocyte proliferation. This activity is due to the presence of multiple inhibitors, one of which appears to be IL-2 related; at least part of the inhibitory activity may be due to elevated serum levels of APP.
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PMID:Multiple inhibitors of mitogen-induced proliferation of normal lymphocytes in juvenile chronic arthritis sera. 212 29

The production of collagenase by human articular chondrocytes in response to interleukin-1 beta is inhibited in a dose-dependent manner by interferon-gamma (1-1,000 units/ml). The analysis of culture medium samples by Western blotting and the measurement of levels of tissue inhibitor of metalloproteinases suggest that the decrease in measurable collagenase activity is primarily due to the inhibition of procollagenase production. These results provide evidence of a role for interferon-gamma in limiting connective tissue degradation.
Arthritis Rheum 1990 Nov
PMID:Inhibition of interleukin-1-induced collagenase production in human articular chondrocytes in vitro by recombinant human interferon-gamma. 217 7

The biological effects of tumor necrosis factor (TNF) include the enhancement of fibroblast proliferation, the secretion of collagenase and prostaglandin E2 (PGE2) by fibroblasts, and the resorption of bone and cartilage, suggesting a role for this cytokine in arthritic conditions. To investigate this, we measured the levels of TNF in synovial fluids and evaluated its secretion by synovial fluid mononuclear cells and tissues from patients with rheumatoid arthritis, osteoarthritis, and seronegative arthritis and normals. TNF was found to be secreted in all arthritic conditions but not in normals. The levels of TNF were highest in synovial fluid and correlated with interferon-gamma (IFN-gamma) levels but not PGE2. The production of TNF was stable in a single joint for 3 to 6 months. Using immunohistochemical staining, TNF was localized to mononuclear cells in the lining layer, sublining, and perivascular areas of synovial tissue. The secretion of TNF by rheumatoid synovial fluid mononuclear cells was inhibited by PGE2, while IFN-gamma enhanced its production in those cells which were spontaneously secreting TNF. Our data suggest that TNF may play a role in various arthritic diseases.
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PMID:Characteristics of tumor necrosis factor production in rheumatoid arthritis. 247 44

We have examined proliferation of and interferon-gamma (IFN-gamma) production by peripheral blood lymphocytes induced by a purified mitogen derived from mycoplasma arthritidis (MAS) in patients with seronegative spondylo-arthropathies and healthy individuals. In all patients and healthy controls MAS exerted a potent nonspecific lymphoproliferation. In contrast, only patients with ankylosing spondylitis (ASp) showed a strong IFN-gamma production after stimulation with MAS. The maximal IFN-gamma response was observed in HLA-B27+/HLA-DQw3+ patients. However, healthy controls with the HLA-DQw3 haplotype with or without the presence of HLA-B27 exhibited also a slight but statistically not significant increase of IFN-gamma production. Moreover, in this study we have found an enhanced frequency of HLA-DQw3 in patients with ASp and reactive arthritis. This immunogenetic association explains the enhanced lymphocyte reactivity in these inflammatory rheumatic disorders to mycoplasmal antigens.
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PMID:Enhanced interferon-gamma production by lymphocytes induced by a mitogen from mycoplasma arthritidis in patients with ankylosing spondylitis. 251 Feb 39

Exuberant tumor-like synovial cell proliferation with invasion of periarticular bone is a feature of rheumatoid arthritis in humans and of streptococcal cell wall (SCW)-induced arthritis in rats. These histologic observations prompted us to examine synoviocytes from arthritic joints for phenotypic characteristics of transformed cells. The capacity to grow in vitro under anchorage-independent conditions is a characteristic that correlates closely with potential in vivo tumorigenicity. In medium supplemented with 20% serum or in basal media supplemented with platelet-derived growth factor (PDGF), early passage synoviocytes from both SCW-induced and rheumatoid arthritic joints formed colonies in soft agarose. Epidermal growth factor (EGF), interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and transforming growth factor-beta (TGF-beta) did not support growth, although EGF enhanced PDGF-dependent growth. On the other hand, TGF-beta, as well as all-trans-retinoic acid, inhibited colony growth. Early passage normal rat and human synoviocytes also grew under the same conditions, but lung, skin, and late-gestation embryonic fibroblast-like cells did not. Considered in the context of other published data our findings provide cogent evidence that synoviocytes, but not other types of fibroblast-like cells, readily acquire phenotypic characteristics commonly associated with transformed cells. Expression of the transformed phenotype in the inflammatory site is likely regulated by paracrine growth factors, such as PDGF and TGF-beta.
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PMID:Anchorage-independent growth of synoviocytes from arthritic and normal joints. Stimulation by exogenous platelet-derived growth factor and inhibition by transforming growth factor-beta and retinoids. 278 99

An autoreactive T cell clone derived from a patient with reactive arthritis, two alloreactive T cell lines, two antigen-specific T cell lines and allogeneic resting T cells were analyzed for their responses to monocytes and macrophages derived from monocytes by in vitro differentiation. The autoreactive T cell clone strongly proliferated in response to fresh monocytes and to macrophages derived from a 7 day culture, but only poorly to monocytes cultured for 2 days. In contrast, alloreactive and antigen-specific T cell lines proliferated to all stimulatory cells equally well. Finally, primary mixed lymphocyte reactions could be stimulated by both fresh and 2-day cultured monocytes, but not by in vitro derived macrophages. The impaired response of the autoreactive T cell clone to 2-day cultured monocytes could not be attributed to reduced expression of several well-defined surface molecules nor to induction of nonresponsiveness. Neither allogeneic monocytes nor cytokines (IL-1, IL-2, IL-4, IL-6) could correct the defective response of the autoreactive T cell clone. However, preculture of monocytes in the presence of interferon-gamma, IL-1, IL-4 or IL-6 retained their stimulatory capacity. Our interpretation of the selectively impaired response of the autoreactive T cell clone is that it most likely recognizes a differentiation-dependent monocyte/macrophage-specific peptide.
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PMID:Monocyte differentiation and accessory function: different effects on the proliferative responses of an autoreactive T cell clone as compared to alloreactive or antigen-specific T cell lines and primary mixed lymphocyte cultures. 752 57

Hyaluronanreceptor (CD44) has been shown to be involved in lymphocyte homing during normal leucocyte circulation and during leucocyte extravasation into sites of tissue inflammation. In addition, interaction with CD44 molecule induces T-cell activation and production of cytokines, such as interferon-gamma. In this study we have examined what influence interaction with the CD44 receptor would have on collagen II-induced arthritis in mice. Mice were immunized with rat collagen II and administered with injections of a monoclonal anti-CD44 antibody. Seventeen days after the outbreak of the disease, all of the anti-CD44 treated animals remained clinically health, whereas 37% of the controls displayed arthritis (P < 0.001). Ten days later the prevalence of arthritis was 26% and 65% (P < 0.05), respectively. Furthermore, the severity of the arthritis was significantly ameliorated by the anti-CD44 treatment. Serum levels of interferon-gamma were significantly higher in collagen II immunized animals having been treated with anti-CD44, compared to the controls. Delayed-type hypersensitivity (DTH) response was significantly decreased in the anti-CD44 treated animals, indicating a functional suppression of T cells. In contrast, T cell independent experimental inflammation was not affected by the administration of CD44 antibodies. Our results suggest that interaction with CD44 down-regulates T lymphocyte/monocyte mediated inflammatory reaction, possibly by triggering of interferon-gamma release.
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PMID:Administration of antibodies to hyaluronanreceptor (CD44) delays the start and ameliorates the severity of collagen II arthritis. 754 11

Immunization of BALB/c mice with human fetal cartilage proteoglycan (PG) produces progressive polyarthritis, and T cells play key roles in the development of the disease. To gain an understanding of how PG is presented to autoreactive T cells by synovial antigen-presenting cells (APC), we examined the abilities of various syngeneic APC in presenting PG to a specific T cell hybridoma 5/4E8, derived from a mouse with PG-induced arthritis. A20 B lymphoma cells and spleen cells were strong presenters of PG, but synoviocytes and P388D1 macrophages could only present PG effectively after stimulation with interferon-gamma (IFN-gamma). The IFN-gamma exerted its effect by up-regulating both MHC class II and intercellular adhesion molecule-1 (ICAM-1) expression by these cells as neutralizing antibodies to Ia, LFA-1 and ICAM-1 inhibited presentation. Our studies also showed that synoviocytes and spleen cells took up and processed PG more rapidly than the cell lines. Cysteine and serine protease-dependent antigen presentation of PG was blocked at 4 degrees C, 18 degrees C and by chloroquine treatment, indicating that presentation required active uptake and processing in an acidic compartment, probably in lysosomes. Also, keratan sulphate-depleted and cyanogen bromide (CNBr) and 2-nitro-5-thiocyanobenzoic acid (NTCB)-cleaved PG elicited stronger T cell responses, as they were more easily processed than the native molecule. Furthermore, CNBr-generated peptides were presented by fixed APC, indicating that core protein fragments of cartilage PG can be presented directly by APC in context with MHC class II molecules.
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PMID:Presentation of cartilage proteoglycan to a T cell hybridoma derived from a mouse with proteoglycan-induced arthritis. 769 8


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