Inhibitor of interleukin‐2 in rheumatoid synovial fluid

Miossec, Pierre; Kashiwado, Takamichi; Ziff, Morris

doi:10.1002/art.1780300201

Cited by 45 publications

(15 citation statements)

References 33 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RA synovial T cells have markedly diminished responses to lectins (75,79,83), to autologous non-T cells (83) and to soluble anti-CD3 (87). These defective responses have been attributed to inhibitors of IL-1 action (87), or of IL-2 production and function (90,91). Despite these findings, elevated levels of soluble IL-2R have been found in RA synovial fluid (92), which, along with surface expression of class II MHC molecules (23,24) suggests that T cell activation has occurred.…”

Section: Resultsmentioning

confidence: 99%

Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen.

Fox

Millard

et al. 1990

J. Clin. Invest.

View full text Add to dashboard Cite

Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw6O). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on

show abstract

Section: Resultsmentioning

confidence: 99%

Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen.

Fox

Millard

et al. 1990

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…This low percentage, despite the high number of T helperhnducer lymphocytes and HLA-DR positive cells, could be explained by either the fragility of the receptor or, more probably, the suppression of IL-2 production that is often seen in RA (30,31). Indeed, an inhibitor of IL-2 has been detected in the synovial fluid of patients with RA (32,33). This factor suppresses the production of IL-2 by human lymphocytes, and it was shown to inhibit the proliferation of IL-2-stimulated murine T cell lines.…”

Section: Discussionmentioning

confidence: 99%

Synovial membrane histology and immunopathology in rheumatoid arthritis and osteoarthritis. In vivo effects of antirheumatic drugs

Haraoui

Pelletier

Cloutier

et al. 1991

Arthritis & Rheumatism

155

View full text Add to dashboard Cite

We examined the histologic and immunopathologic features of the synovial membrane of 18 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthritis (OA) who had undergone total knee arthroplasty. Patients were classified into 5 groups according to therapeutic regimen and disease: RA treated with nonsteroidal antiinflammatory drugs (NSAIDs), RA treated with NSAIDs and prednisone, RA treated with NSAIDs and methotrexate (MTX), OA treated with analgesics, and OA treated with NSAIDs. There were no significant between‐group differences in the percentages or the distribution pattern of the infiltrating T cell subsets (CD4, CD8), HLA–DR, or interleukin‐2 receptor‐bearing cells. However, inflammatory indices, which included the thickness of the lining cell layer and the density of the mononuclear cell infiltrate, were significantly higher in the RA patients treated with prednisone and those treated with MTX (P < 0.05). Similarly, fibrosis was markedly reduced in these 2 groups. The RA patients treated with NSAIDs alone and the 2 groups of patients with OA demonstrated similar profiles. These data suggest that prednisone and MTX may inhibit the development of fibrosis without altering the subsets of the inflammatory cell population. This observation raises the possibility that the action of these 2 drugs may be partly mediated by the suppression of inflammatory mediators that are responsible for fibroblast activation.

show abstract

“…Indomethacin, which blocks prostaglandin synthesis, also increased IL 2 production by RA cells (3). Both IL 1 (29) and IL 2 (30) inhibitors have been suggested as the cause ofthe low IL 2 production in RA.…”

Section: Discussionmentioning

confidence: 99%

Increased polyamines may downregulate interleukin 2 production in rheumatoid arthritis.

Flescher¹,

Bowlin²,

Ballester³

et al. 1989

J. Clin. Invest.

View full text Add to dashboard Cite

Polyamines downregulate immune reactivity. RA is associated with decreased IL 2 production. In this study, we present evidence to suggest that excessive polyamines can contribute to the IL 2 deficiency in RA. Blocking polyamine production with inhibitors of ornithine decarboxylase results in increased IL 2 production by RA PBMC. Moreover, polyamine oxidase (PAO) inhibitors and catalase also increase IL 2 production by RA PBMC. This effect of PAO inhibition is monocyte mediated.After 3 d in culture, RA PBMC produce three times more IL 2 than do normal PBMC. This rise is prevented by exogenous spermidine but only in the presence of monocytes. The concentration of polyamines in RA PBMC and synovial fluid MNC is 2-20-fold higher than in normal cells.Thus, polyamines and their oxidation products downregulate IL 2 production by RA PBMC and may account for the decreased T cell effector function seen in this disease.

show abstract

Inhibitor of interleukin‐2 in rheumatoid synovial fluid

Cited by 45 publications

References 33 publications

Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen.

Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen.

Synovial membrane histology and immunopathology in rheumatoid arthritis and osteoarthritis. In vivo effects of antirheumatic drugs

Increased polyamines may downregulate interleukin 2 production in rheumatoid arthritis.

Contact Info

Product

Resources

About