Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effect of endogenous prostaglandin E2 (PGE2) on interleukin 1 (IL-1) production by peripheral blood monocytes from patients with rheumatoid arthritis (RA). IL-1 production by RA monocytes was not different from that of monocytes from normal controls, when the cells were either unstimulated or stimulated with lipopolysaccharide (LPS, 20 micrograms/ml), as measured by two different bioassays (thymocyte or fibroblast proliferation assay) and enzyme-linked immunosorbent assay. However, IL-1 production by LPS-stimulated monocytes from RA patients cultured in medium containing indomethacin, an inhibitor of PGE2 synthesis, was significantly greater than that of monocytes from normal controls. In addition, the levels of PGE2 in culture supernatants of unstimulated or LPS-stimulated monocytes from RA patients were higher than in culture supernatants of monocytes from normal controls. Moreover, the increase of in vitro IL-2 production by RA T cells stimulated by phytohemagglutinin (PHA) was observed when monocytes were removed from peripheral blood mononuclear cells. These results indicated that peripheral blood monocytes from RA patients could produce IL-1 in excess in vitro, but that in vivo IL-1 production by RA monocytes and IL-2 induction by RA T cells might be negatively regulated by endogenous PGE2.
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PMID:Role of endogenous prostaglandin E2 in interleukin 1 production by peripheral blood monocytes from patients with rheumatoid arthritis. 233 Aug 42

To clarify the interactions between mononuclear cells and polymorphonuclear leukocytes, and to identify the cytokine(s) that mediate the interaction, the effects of a culture supernatant of LPS-stimulated mononuclear cells on production of arachidonic acid metabolites of polymorphonuclear cells were studied. The culture supernatant of LPS-stimulated mononuclear cells increased production of prostaglandin E2 of polymorphonuclear cells. TNF alpha, but not IL-1, IL-2, IL-6, or IFN gamma, enhanced the prostaglandin E2 production when added in vitro. Additionally, an anti-rTNF alpha monoclonal antibody inhibited the stimulating activity of the culture supernatants. TNF alpha, produced by mononuclear cells, appears to play an important role in the development of inflammation, such as rheumatoid arthritis, by enhancing the arachidonic acid metabolism of the polymorphonuclear cells.
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PMID:Mononuclear cells enhance prostaglandin E2 production of polymorphonuclear leukocytes via tumor necrosis factor alpha. 233 39

Compound IX 207-887 is a novel antiarthritic agent which inhibits the release of interleukin-1 (IL-1) from human monocytes and mouse peritoneal macrophages in vitro at concentrations which are achieved therapeutically in human rheumatoid arthritis and in animal models of arthritis. In the present studies IL-1 activity in conditioned media, homogenates or lysates was monitored using four independent assay systems. Biologically active IL-1 was determined by, a) the induction of latent metalloproteinase-release from rabbit articular chondrocytes, which is relatively specific for IL-1 and b) by a sensitive thymocyte proliferation assay. Immunoreactive IL-1-beta was assayed by RIA and ELISA. In all test systems IX 207-887 significantly reduced both biologically active and immunoreactive IL-1 in culture media, whereas the levels of IL-1 in homogenates or lysates were either unaffected or only marginally reduced. The release of other monokines tested, such as interleukin-6 and tumour necrosis factor-alpha, and the secretion of lysozyme were only marginally influenced. IX 207-887 neither affected the adherence of human monocytes nor markedly inhibited IL-1 or IL-2-induced thymocyte proliferation. In the chondrocyte test no IL-1 antagonistic activity of IX 207-887 could be observed. All of these data indicate that IX 207-887 has the novel property of being an inhibitor of IL-1 release.
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PMID:Inhibition of interleukin-1 release by IX 207-887. 238 8

Since interleukin-4 (IL-4) displays agonistic effects on both T and B cells, we studied whether this lymphokine is involved in rheumatoid synovitis, a disease characterized by intense T cell infiltration and B cell stimulation. Rheumatoid arthritis synovial fluids (RA SF) contained no (less than 15 pg/ml) or very low amounts (less than 25 pg/ml) of IL-4, as measured by a sensitive and specific enzyme-linked immunosorbent assay. No IL-4 was produced by unstimulated rheumatoid synovial membrane. RA SF were found to inhibit phorbol myristate acetate (PMA)-dependent proliferation of normal peripheral blood lymphocytes (PBL). An inhibitory fraction with an apparent molecular weight of 150 kd was isolated by gel filtration. The inhibitory fraction strongly blocked the proliferation of PBL induced by PMA, PMA + IL-2, or PMA + IL-4. However, this fraction was less effective in blocking the proliferation of PBL induced by PMA + IL-2 + IL-4. High levels of transforming growth factor beta (TGF beta) were found in these RA SF, and an anti-TGF beta antibody was able to partially reduce the inhibitory activity. RA SF were found to inhibit phytohemagglutinin-induced IL-4 production by PBL. These data indicate that IL-4, similar to other T cell lymphokines, cannot be detected in RA SF and that RA SF contains an inhibitory activity, related in part to TGF beta, which blocks mitogen-induced proliferation of PBL, at least in part through an inhibition of T cell-derived lymphokine release.
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PMID:Low levels of interleukin-4 and high levels of transforming growth factor beta in rheumatoid synovitis. 239 Jan 23

Gangliosides were evaluated for their ability to inhibit the phenotype and function of an encephalitogenic T-helper lymphocyte line from Lewis rats (BP-1), which responds specifically to guinea pig myelin basic protein (GP-BP). After activation for 3 days with GP-BP, the BP-1 line induced a lethal form of experimental autoimmune encephalomyelitis (EAE) in recipient rats 3-6 days after intraperitoneal injection. Incubation of activated BP-1 line cells with 250 microM gangliosides for 1 hr prior to injection prevented EAE completely in 5/14 recipients and markedly reduced the severity of clinical signs and histologic lesions in the rest. Similar treatment of BP-1 cells with galactocerebroside had no inhibitory effect. Both individual and mixed gangliosides inhibited accessory cell-dependent activation of BP-1 cells with GP-BP. Gangliosides also inhibited BP-1 activation with a cell-free supernatant containing accessory cell-processed GP-BP and rat Ia molecules, suggesting that the inhibition was not restricted to accessory cell function. In addition to inhibiting antigen-dependent proliferation, gangliosides inhibited IL-2 dependent cell growth. Furthermore, individual and mixed gangliosides blocked binding of anti-T-helper cell antibody (W3/25) to the BP-1 line, while galactocerebroside, ceramide, and sialic acid had no inhibitory effect. Cell surface staining of T-total, T-non-helper, or Ia determinants was relatively unaffected by gangliosides. Taken together, the immunomodulatory properties of gangliosides on T-effector cell function lend biologic importance to the increased levels of gangliosides which have been reported in human diseases with immunoregulatory abnormalities such as multiple sclerosis, rheumatoid arthritis, and cancer.
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PMID:Gangliosides inhibit phenotypic and functional properties of an encephalitogenic T-helper lymphocyte line. 241 33

Purified podophyllotoxin (CPH-86) is an inhibitor of microtubular aggregation used in the treatment of cancer, psoriasis and rheumatoid arthritis. To better understand its immunopharmacology we examined its effects on human lymphocytes and monocytes and guinea pig macrophages. CPH-86 inhibits mitogen-induced human lymphocyte proliferation and macrophage growth factor-stimulated macrophage proliferation with ID50s of approximately 10(-7) M. The effect of CPH-86 on lymphocytes in conjunction with mitogen is nonlethal, evident during the early but not the late phases of proliferation, and associated with early increases in cyclic AMP levels. In contrast to these obviously inhibitory effects, CPH-86 (10(-7) M) alone induces IL-1 by human monocytes and, with mitogen, it induces IL-2 production by human lymphocytes. It directly stimulates macrophage proliferation and potentiates the effects of low doses of macrophage growth factor to do so. The latter effects may be mediated by colony stimulating factor production. The effects of CPH-86 are not mediated by inhibition of prostaglandin synthesis. The stimulation of monokine and lymphokine production by CPH-86 may represent positive features of its action and may be immunotherapeutic.
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PMID:Purified podophyllotoxin (CPH-86) inhibits lymphocyte proliferation but augments macrophage proliferation. 244 10

Kinins are vasoactive peptides whose potent inflammatory and bone resorbing properties suggest a role for these autacoids in the pathogenesis of inflammatory arthritis. We used cultured human synovial cells as a model to evaluate the effects of bradykinin on articular tissue. In resting synovial cells, bradykinin was a relatively ineffective stimulus for PGE2 production. However, after a period of preincubation with the cytokine, IL-1, which is itself a stimulus for PGE2 production, synovial cells exhibited a further striking time- and dose-dependent response to bradykinin. Maximal release of PGE2 was observed in response to 10(-7) to 10(-6) M bradykinin after first pretreating the cells for 24 h with 5 to 10 U/ml of IL-1. rIL-1 alpha and IL-1 beta, as well as rTNF-alpha, induced a similar response to bradykinin in synovial cells, whereas recombinant IL-2 did not. The bradykinin analog, lysylbradykinin, was equipotent in inducing PGE2 release from IL-1 pretreated synovial cells, whereas des(Arg9) bradykinin, substance P, and neurokinins A and B were ineffective in this regard in both IL-1-pretreated and in resting cells. Synovial cells derived from patients with rheumatoid arthritis and osteoarthritis responded similarly to bradykinin. The synergistic response in PGE2 production induced by IL-1 and bradykinin was significantly inhibited by pretreatment with 1 microM indomethacin or dexamethasone (96 and 94% inhibition, respectively). In addition, the response was abrogated by pretreatment with 10 micrograms/ml of cycloheximide or actinomycin D (81 and 97% inhibition, respectively). These data provide the first description of synergism of IL-1 with a noncytokine peptide in human synovial cells. The ability of IL-1 to increase the responsiveness of synovial tissues to bradykinin may play an important role in potentiating inflammatory responses within the joint.
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PMID:Preincubation of human synovial cells with IL-1 modulates prostaglandin E2 release in response to bradykinin. 247 45

Double-marker assays were developed for enumerating CD5+ B-cells and CD25+ activated B-cells. To measure CD5+ B-cells, CD19+ (pan B-specific) cells were first isolated from peripheral blood mononuclear cells using anti-Leu12-coated immunomagnetic beads (Dynabeads). Positively selected cells were stained for surface immunoglobulin (sIg) and then incubated with anti-Leu1-coated Dynabeads. Fluorescent cells which also bound Dynabeads could be readily enumerated. The proportion of CD5+ B-cells was found to be significantly elevated in 9 of 20 patients with definite rheumatoid arthritis. B-cells bearing the interleukin-2 receptor (IL-2-R, CD25) were identified in pokeweed mitogen-stimulated PBM by sIg fluorescence and rosetting with anti-Tac-labelled Dynabeads. The kinetics of CD25 expression following activation were found to be different for B- and non-B-cells.
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PMID:Double-marker analysis of B lymphocyte subsets using a combination of immunofluorescence and rosetting with immunomagnetic beads. 248

Granulocyte/macrophage CSF (GM-CSF) has recently been identified in rheumatoid arthritis (RA) synovial effusions. To study a potential role for GM-CSF and other cytokines on the induction of HLA-DR expression on monocytes and synovial macrophages, we analyzed the relative ability of recombinant human cytokines to induce the surface expression of class II MHC antigens on normal peripheral blood monocytes by FACS analysis. GM-CSF (800 U/ml) (mean fluorescence channel 2.54 +/- 0.33 times the control, p less than 0.001) and IFN-gamma (100 U/ml) (5.14 +/- 0.60, p less than 0.001) were the most potent inducers of HLA-DR. TNF-alpha and IL-4 also increased HLA-DR expression, although to a lesser degree [1.31 +/- 0.06 (p less than 0.02) and 1.20 +/- 0.03 (p less than 0.01), respectively]. IL-1 (40 U/ml), IL-2 (10 ng/ml), IL-3 (50 U/ml), IL-6 (100 U/ml), and CSF-1 (1,000 U/ml) did not affect surface HLA-DR density. GM-CSF also increased HLA-DR mRNA expression and surface HLA-DQ expression, but decreased CD14 (a monocyte/macrophage antigen) expression. The effect of GM-CSF on HLA-DR was not mediated by the generation of IFN-gamma in vitro because it was not blocked by anti-IFN-gamma mAb. GM-CSF was additive with IL-4 and low amounts (less than 3 U/ml) of IFN-gamma and synergistic with TNF-alpha. Because we have recently reported that supernatants of cultured RA synovial cells produce a non-IFN-gamma factor that induces HLA-DR on monocytes, we then attempted to neutralize this factor with specific anti-GM-CSF mAb. Four separate synovial tissue supernatants were studied, and the antibody neutralized the HLA-DR-inducing factor in each (p less than 0.01).
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PMID:Cytokines in chronic inflammatory arthritis. IV. Granulocyte/macrophage colony-stimulating factor-mediated induction of class II MHC antigen on human monocytes: a possible role in rheumatoid arthritis. 250 78

We studied the hypoproliferative response of synovial fluid (SF) T cells in rheumatoid arthritis (RA) using a mitogenic monoclonal antibody (MoAb) specific for the T-cell antigen receptor-associated CD3 complex. RASF T cells are defective in their proliferative response and in the induction of the Tac (p55) component of the IL-2-receptor (IL-2-R) when stimulated with anti-CD3 monoclonal antibody (MoAb). However, fresh RASF T cells bear demonstrable IL-2-R in cross-linking experiments which are not seen in unstimulated peripheral blood (PB). These receptors are functional since RASF T cells proliferate in response to recombinant IL-2 (rIL-2) better than fresh PB T cells from either normal or RA patients. Scatchard analysis indicates increased (4-fold) numbers of high affinity IL-2-R on (phytohaemagglutinin) PHA-activated RASF T cells as compared with comparably activated RAPB T cells. Phorbol myristate acetate (PMA) induces Tac antigen expression in RASF but does not lead to proliferation. The hyporesponsiveness of RASF T cells does not appear to result from lack of IL-2-R, lack of IL-2-R inducibility, or proliferative potential.
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PMID:Characterization of the IL-2-receptor on rheumatoid arthritis synovial fluid T cells. 253 3


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