UMLS:C0003873 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0003873 (rheumatoid arthritis)
53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regarding of microbiological aspects of arthritis three forms of joint diseases are under investigation: the septic arthritis, the reactive arthritis and the Rheumatoid Arthritis. In 95% of patients with septic arthritis microorganisms as causative agents responsible for the disease are described: Staphylococci, Streptococci, some gram-negative bacteria. By an haematogenic route of infection predominantly patients with immunosuppressive therapy are altered. In newborns and children septic arthritis is to observe more rarely. A reactive arthritis is a postinfectious sterile process in dependence on an infection occurred at an earlier time. As etiologic agents Yersinia, Enterobacteriaceae and Campylobacter have been discovered. 80% of the patients suffering such a reactive arthritis are carrier of the HLA-B27 system. The etiology of the Rheumatoid Arthritis is an open, unanswered problem. Of importance are: immunogenetic conditions, autoimmune phenomena, endocrinologic, dietetic and psychologic factors as well as bacteria and viruses as causative agents: cocci, bacilli, Diphteroids, endoparasitic bacteria (Listeria, L-forms, Mycoplasma, Chlamydiae), viruses (Adeno-, Mumps-, Measles-, ECHO-, Coxsackie-A- and B-, Hepatitis-, Cytomegalo-, Para-influenza-, Retro-, Parvo- and Rubella viruses). In the last years the EBV is of interest covering the question of a distinct virus persistence in tissues and the adequate limiting factors. Perhaps a defect of the hu-IFN-gamma-system might be of immunopathological and clinical significance.
...
PMID:[Microbiologic aspects of inflammatory joint diseases]. 367 41

Moderate titres of antiviral activity were demonstrated in 48-58% of sera obtained from patients suffering from seropositive and seronegative rheumatoid arthritis (RA), psoriatic arthritis, Reiter's syndrome, ankylosing spondylitis, and juvenile rheumatoid arthritis. Sera from blood donors and from patients with various noninflammatory diseases were positive in 16% of cases. The activity was species-specific, mediated by the homologous cells, and destroyed by treatment with trypsin and exposure to pH 2. Antibodies against human IFN-alpha did not neutralise the activity. These characteristics are compatible with those of IFN-gamma or immune interferon. Neither the presence nor the titre of IFN was correlated with disease activity defined by concentration of C-reactive protein, C3 concentration, and erythrocyte sedimentation rate. IFN-gamma was present in 4 of 10 synovial fluids from patients with RA. The titre in one of these was higher than in the corresponding serum, indicating local production in the rheumatoid joint.
...
PMID:Immune interferon in serum and synovial fluid in rheumatoid arthritis and related disorders. 641 86

Oral administration of autoantigens suppresses development of autoimmunity in several animal models, and is being tested in clinical trials in patients with autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Non-obese diabetic (NOD) mice spontaneously develop insulin-dependent diabetes mellitus at 15 to 20 weeks of age, after mononuclear cell (MNC) infiltration of the pancreatic islets of Langerhans and destruction of insulin-producing beta cells. We have previously shown that oral administration of insulin suppresses insulitis and development of diabetes in the NOD mouse. Oral insulin has no metabolic effect on blood glucose. Oral insulin mediates its effect through a T cell-dependent mechanism as shown by adoptive transfer and T cell depletion experiments, but the mechanisms responsible have not been fully explored. We now report a serial analysis of the cells and cytokines associated with development of diabetes in NOD mice, and contrast this with the findings in animals fed equine insulin or a control protein (ovalbumin). Animals were fed 1 mg twice a week for 5 weeks, beginning at 5 weeks of age. Marked insulitis in naive or ovalbumin-fed NOD mice occurred at 10 weeks, at which time a dense peri-islet and intra-islet MNC infiltration was observed. Immunohistological studies using monoclonal antibodies showed that infiltrating MNC consisted mainly of CD4+ T cells ( > 75% of leukocytes) plus smaller numbers of macrophages and CD8+ T cells. These cells displayed evidence of immune activation with expression of receptors for interleukin-2 (IL-2R) plus Th1 cytokines; dense labeling for IFN-gamma and tumor necrosis factor-alpha, plus lesser amounts of IL-2, was observed. MNC lacked labeling for IL-4, IL-10, prostaglandin-E, or transforming growth factor-beta. By contrast, at 10 weeks, pancreatic tissues from NOD mice fed insulin showed considerably less insulitis, and the residual MNC, although still largely CD4+ T cells plus macrophages, showed dense labeling for IL-4, IL-10, prostaglandin-E, and transforming growth factor-beta and an absence of IL-2, IFN-gamma or tumor necrosis factor-alpha Taken together with our previous findings, these data indicate that oral administration of insulin affects the development of diabetes in NOD mice through the generation of cells that elaborate immunoregulatory cytokines within the target organ and shift the balance from a Th1 to a Th2 pattern of cytokine expression.
...
PMID:Suppression of insulitis in non-obese diabetic (NOD) mice by oral insulin administration is associated with selective expression of interleukin-4 and -10, transforming growth factor-beta, and prostaglandin-E. 748 82

Rheumatoid synovitis is characterized by an infiltration of mononuclear cells and by the proliferation of synoviocytes. Monocytes and synoviocytes are major producers of cytokines, growth factors, and enzymes that contribute to the rheumatoid arthritis (RA) process. Since they are in close contact in vivo, we engaged in an in vitro study of the functional consequences of their interactions. Coculture of unstimulated elutriated normal blood monocytes over RA synoviocytes resulted in a synergistic increase of the production of IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), leukemia inhibitory factor (LIF), and IL-8, when compared with their respective production in culture alone. In contrast, cytokines such as IL-10, IL-1 beta, IL-1 alpha, and TNF-alpha could not be detected. The IL-6 production in coculture was further increased by the addition of IL-1 beta, GM-CSF, IFN-gamma, or TNF-alpha, but was inhibited by the addition of IL-10, IL-4, IL-13, or IL-1Ra, an effect reverted by the addition of IL-1 beta. Moreover, an inhibition was also observed with anti-CD14 mAb and newly raised mAbs directed against RA synoviocytes. Under reducing conditions, the mAb SY12 precipitated a 150-kDa surface membrane protein, identified as amino-peptidase N (CD13/AP-N). Collectively, these results indicate that 1) monocytes and synoviocytes interact with each other to produce proinflammatory cytokines, 2) pro- and antiinflammatory cytokines have opposite effects on IL-6 production, and 3) molecules such as IL-1, CD14, and CD13 are involved.
...
PMID:Contribution of IL-1, CD14, and CD13 in the increased IL-6 production induced by in vitro monocyte-synoviocyte interactions. 756 Oct 64

Type II collagen-induced arthritis (CIA) is an animal model of inflammatory polyarthritis with clinical and pathological features resembling rheumatoid arthritis (RA). We compared the expression of T cell receptor (TCR) V beta genes in T cells isolated from the inflamed joints, draining lymph nodes and the spleens of BUB/BnJ (H-2q) mice (BUB) during the early phase of CIA. We also investigated the profiles of cytokine gene expression in T cells obtained from the same tissues. We found that the expression of TCR V beta s, in arthritic joints of mice, during the early phase of the disease was limited to TCR V beta 3 and 10 gene families. In contrast, TCR V beta 4, 7, and 15 were predominant in the draining lymph nodes (LNs) and TCR V beta 2, 6, and 14 were predominant in the spleens of arthritic mice. Molecular cloning and sequence analysis revealed that the T cell populations in the arthritic joints were oligoclonal as determined by the limited N-D-N region diversity observed in the sequenced clones. These results demonstrate, for the first time, that (1) joint infiltrating T cells in TCR V beta a genotype mice use a restricted repertoire of TCR V beta genes; (2) there was oligoclonal expansion of infiltrating T cells in arthritic joints in mice with collagen-induced arthritis. Our results on cytokine gene expression in the arthritic joints of BUB mice indicate that Th-1-like T cell derived cytokines may be the predominant cytokines in the arthritic joints as illustrated by the presence of transcripts for IL-2 and IFN-gamma but not IL-4. In summary, our results provide evidence that T cells with restricted specificities, and more specificially, Th-1 type T cells, are crucial in the early phase of collagen induced arthritis in mice.
...
PMID:Restricted expression of T cell receptor V beta and lymphokine genes in arthritic joints of a TCR V beta a (H-2q) mouse strain-BUB/BnJ-with collagen-induced arthritis. 757 77

The current studies examined whether cytokine patterns indicative of an imbalance in Th1 and Th2 cells could be identified in PBMC of patients with active rheumatoid arthritis (RA). To investigate this possibility, a reproducible PCR technique to assess cytokine mRNA levels in PBMC was employed that minimized in vitro manipulation of the cells. Seven of 14 RA patients had increased mRNA levels for IL-2, 5/14 for IFN-gamma, 3/14 for IL-4, and 4/14 for the IL-2R alpha-chain, compared with normal donors. Whereas 4 patients had elevated mRNA for IL-2 and IFN-gamma, indicative of an increase in activated Th1 or Th0 cells, 1 of 14 patients expressed low levels of IL-2 and IFN-gamma and high levels of IL-4 mRNA. Seven RA patients were treated with a mAb to ICAM-1 (CD54). To determine whether changes in cytokine mRNA levels might be associated with and/or account for the anti-inflammatory effect of anti-ICAM-1 mAb therapy, changes in cytokine mRNA levels were assessed and correlated with clinical improvement. Anti-ICAM-1 mAb administration was followed by a prompt and transient increase of IFN-gamma mRNA. Elevation of IFN-gamma mRNA expression throughout the treatment period reflected a temporary increase in the number of circulating CD3+CD4+ T cells, suggestive of altered circulatory patterns of activated Th1-like cells and was related to clinical efficacy. The results indicate that elevated cytokine mRNA levels characteristic for Th1 cells can be detected in the PBMC in active RA and, furthermore, that anti-ICAM-1 mAb may be beneficial in RA by altering the recruitment of activated Th1-like cells into the synovium. This assumption further strengthens the hypothesis of a significant contribution of Th1-like cells to the pathogenesis of RA.
...
PMID:Elevated Th1- or Th0-like cytokine mRNA in peripheral circulation of patients with rheumatoid arthritis. Modulation by treatment with anti-ICAM-1 correlates with clinical benefit. 759 11

We recently reported on an inflammatory arthropathy resembling rheumatoid arthritis that develops in high incidence among transgenic mice that carry the env-pX region of the human T cell leukemia virus type 1 genome. In an effort to elucidate the pathogenesis of this disease, we found that genes for inflammatory cytokines, including IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, transforming growth factor-beta 1, IFN-gamma, and IL-2, as well as MHC genes were activated in transgenic joints. Serum levels of IL-1 beta and IL-6 were also elevated. Interestingly, these mice produced Ab against IgG, type II collagen (IIC), and heat shock proteins accompanied by IgG hypergammaglobulinemia. The cellular immune response to IIC as well as that to heat shock proteins were activated. Moreover, these mice became immunologically responsive to exogenously administered IIC and developed arthritis, in contrast to their nontransgenic littermates, which showed little response to IIC. Taken together, the results suggest that human T cell leukemia virus type 1 can cause immune system hyperreactivity and induce autoimmunity. The possibility that elevated cytokine and/or MHC gene expression are involved in the development of autoimmunity and arthropathy are discussed.
...
PMID:Autoimmunity induction by human T cell leukemia virus type 1 in transgenic mice that develop chronic inflammatory arthropathy resembling rheumatoid arthritis in humans. 763 19

In the blood of patients with rheumatoid arthritis and/or sclerodermia systematica usually acid-labile interferon-alpha (IFN-alpha) was found. Blood leukocytes cannot be considered the source of its production as they spontaneously produce IFN-gamma identified with specific antiserum. Blood leukocytes of tested patients generated in vitro a reduced amount of staphylococcus enterotoxin A-induced IFN-gamma and virus-induced acid-labile IFN-alpha. This findings support the assumption of impaired functioning of T- and B-blood cells in autoimmune diseases. The production of Newcastle diseases virus-induced IFN-alpha and influenza virus-induced acid-stable IFN-alpha by patients' leukocytes has not been altered. Acid-labile IFN-alpha obtained from the blood of tested patients, IFN-gamma spontaneously generated by leukocytes in vitro and acid-labile IFN-alpha produced by leukocytes in vitro following induction with influenza virus show similar sensitivity to pH 2.0 and time patterns of the antiviral state development in human diploid fibroblast culture.
...
PMID:Interferon system in patients with rheumatoid arthritis and sclerodermia systematica. 769 10

Monocytes/macrophages and synovial fibroblast-like cells are in intimate contact in the synovium and are believed to play a critical role in the development of rheumatoid arthritis. We investigated the effects of monocyte-synoviocyte interactions in vitro on cytokine release and the expression of adhesion molecules. Using a sensitive Western blot assay, we found that VCAM-1 and ICAM-1 expression were up-regulated in synoviocytes following coculture. The interaction also resulted in the accumulation of TNF and IL-6, but not IFN-gamma in the culture medium. Culture supernatant from monocyte-synoviocyte samples effectively induced adhesion molecules in synoviocytes. Anti-TNF partially inhibited the increase in VCAM-1 and ICAM-1 expression, indicating that TNF in part mediates VCAM-1 and ICAM-1 expression. Interestingly, the induction of cytokines and adhesion molecules did not require cell contact between monocytes and synoviocytes, suggesting cell communication via soluble factors. T cell cytokines enhanced the induction of adhesion molecules induced by the monocyte-synoviocyte interaction. IFN-gamma and IL-4, which are produced by distinct T helper subsets, had differential effects on monocyte-synoviocyte interactions. IFN-gamma had a minimal effect on VCAM-1 expression by synovial fibroblasts, but synergized with monocytes to dramatically up-regulate ICAM-1 expression. IL-4 had no effect on ICAM-1 expression but enhanced monocyte-induced expression of VCAM-1. Our results demonstrate that the up-regulation of adhesion molecules following monocyte-synoviocyte interactions is mediated by soluble factors and can be regulated by specific T cell cytokines.
...
PMID:Interacting monocytes and synoviocytes induce adhesion molecules by a cytokine-regulated process. 769 87

Dysregulated cytokine production, in particular of the monokines IL-1, IL-6, and TNF, has been implicated in the inflammatory response in rheumatoid arthritis and in promoting the ensuing tissue destruction. The 3-substituted 2-oxindole tenidap has proven anti-inflammatory actions both in vivo and in vitro, among which is the inhibition of TNF and IL-1 production by monocytes following activation by LPS. We have investigated this ability to modulate cytokine activity by studying its effects on cytokine-monocyte interactions and in particular IL-6 production, with the THP-1 monocyte cell line. Tenidap inhibited IL-6 production in a dose-dependent manner when cells were stimulated with a combination of TNF-alpha and IFN-gamma. It also inhibited the priming effect of IFN-gamma, preventing the super-induction of IL-6 production following subsequent stimulation with TNF-alpha and IFN-gamma. These effects occurred under conditions in which the cells were not irreversibly altered with respect to their protein synthetic activity. IFN-gamma-induced up-regulation of HLA-DR was also inhibited by tenidap. Tenidap appears to affect some aspect of the IFN-gamma activation pathway, possibly the differentiation of these immature monocytes to a more mature phenotype. The data presented here indicate that tenidap has the potential to modulate the cytokine network in chronic disease.
...
PMID:Tenidap-modulated proinflammatory cytokine activation of a monocyte cell line. 773 Jun 39

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>