Monocyte activation in early onset rheumatoid arthritis.

Fujii, I; Sato, Masao; Nobunaga, Masashi

doi:10.1136/ard.49.7.497

Cited by 35 publications

(11 citation statements)

References 37 publications

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“…There was, however, no correlation between IL-1p mRNA levels and indicators of clinical disease activity. Whereas it has been reported that serum levels of IL-1 correlate with clinical indicators of disease activity in RA (7,24), no such correlation was found between these indicators and spontaneously secreted IL-1 from peripheral blood monocytes in vitro (25). Together, these results suggest that a considerable proportion of IL-1 found in the serum may be produced by cells that are not found among the PBMC, such as activated macrophages within the synovial tissue.…”

Section: Discussioncontrasting

confidence: 63%

Elevated cytokine messenger RNA levels in the peripheral blood of patients with rheumatoid arthritis suggest different degrees of myeloid cell activation

Schulze‐Koops

Davis

Kavanaugh

et al. 1997

Arthritis & Rheumatism

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Objective. To determine whether monocytes in rheumatoid arthritis (RA) are activated to produce proinflammatory cytokines in the peripheral circulation before entering the synovium and whether the pattern of cytokines that is expressed correlates with disease activity. Methods. Cytokine messenger RNA (mRNA) levels were assessed in peripheral blood mononuclear cells (PBMC) from 14 RA patients and 14 healthy controls by semiquantitative reverse transcription–polymerase chain reaction technology. The method employed was sufficiently sensitive to assess cytokine mRNA levels in freshly isolated cells without the necessity of in vitro stimulation. Thus, an estimate of the in vivo state of activation could be obtained. Results. Interleukin‐8 (IL‐8) mRNA levels were elevated in all 14 RA patients compared with normal controls, whereas 7 of 14 RA patients had elevated levels of mRNA for IL‐6 or IL‐10. IL‐1B mRNA levels were below the normal range in 3 of 14 patients, within normal limits in 4 of 14, and elevated in 7 of 14. Tumor necrosis factor a mRNA levels were within the normal range in 9 of 14 patients and below normal in 5 of 14. There was a statistically significant difference between the mean IL‐10 (P < 0.05) and IL‐8 (P < 0.001) mRNA.levels in RA patients and normal controls. Of note, the 7 patients with elevated IL‐lβ mRNA levels also expressed the highest levels of IL‐8 mRNA. Whereas a strong correlation between the expression of IL‐lβ and IL‐8 mRNA (P < 0.001) was found, expression of all other mRNA occurred independently of each other. Levels of cyclooxygenase 2 (COX‐2) mRNA were also determined to evaluate the status of myeloid cell activation more completely. COX‐2 mRNA levels were within the normal range in 4 of 11 patients and below normal in 7 of 11, but did not correlate with the expression of any of the cytokine mRNA. Conclusion. Elevated levels of mRNA for selected cytokines that are predominantly produced by monocytes can be found in the PBMC of many RA patients. The data indicate that myeloid precursor cells become activated to produce cytokines before they enter the synovium, a finding which emphasizes the systemic nature of RA.

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Section: Discussioncontrasting

confidence: 63%

Elevated cytokine messenger RNA levels in the peripheral blood of patients with rheumatoid arthritis suggest different degrees of myeloid cell activation

Schulze‐Koops

Davis

Kavanaugh

et al. 1997

Arthritis & Rheumatism

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“…The relatively low ratio of immunoreactive IL-Ira to IL-1 likely reflects a combination of high IL-1 production (37) and defective IL-lra production by monocyte-derived cells (30). It should be emphasized that the rheumatoid synovium may contain other molecules that inhibit IL-l activities, such as TGFp or soluble type I1 IL-1R.…”

Section: Il-1 Plays a Central Role In The Pathogenesis Of Rheumatoidmentioning

confidence: 99%

Synovial interleukin‐1 receptor antagonist and interleukin‐1 balance in rheumatoid arthritis

Firestein

Boyle

et al. 1994

Arthritis & Rheumatism

201

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Objective. To quantify interleukin-1 receptor antagonist (IL-lra) and IL-1 production and gene expression by rheumatoid arthritis (RA) synovial tissue (ST) cells.Methods. IL-la, IL-lP, and IL-lra protein levels were measured by enzyme-linked immunosorbent assay in fresh and cultured ST cells, purified synovial macrophages, and fibroblast-like synoviocytes (FLS). The relative expression of the secreted form of IL-lra (sILIra) and the alternatively spliced intracellular form (icIL-lra) was determined by reverse transcription polymerase chain reaction (RT-PCR) techniques.Results. IL-la, IL-lP, and IL-lra were present in fresh and cultured ST cell samples of synovium from RA and osteoarthritis patients. IL-1ra:IL-1 ratios ranged from 1.2 to 3.6, which is below the l&lOO-fold excess of IL-lra needed to inhibit IL-1 bioactivity. Isolated CD14+ synovial macrophages secreted IL-lra, but the amount was much less than that of alveolar or in vitro-derived macrophages. Cultured FLS contained intracellular IL-lra but secreted little IL-lra into the culture supernatants. RT-PCR showed that icIL-lra

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“…MNCs were isolated and cultured as previously described [19]. Twenty milliliters of venous blood treated with heparin were collected, diluted with an equal volume of phosphate buffered saline (PBS) and the MNCs were isolated by Ficoll-Hypaque density gradient centrifugation (Pharmacia Fine Chemicals).…”

Section: Preparation Of Mncsmentioning

confidence: 99%

Synovial fluid and serum levels of soluble interleukin-6 receptor in patients with rheumatoid arthritis

Fujikawa

Sato

Torisu

et al. 1998

Japanese Journal of Rheumatology

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Abstract--Our objective was to measure both synovial fluid (SF) and serum levels of soluble interleukin-6 receptor (slL-6R) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA), and to investigate the amounts of sIL-6R protein produced by cultured synovial cells, chondrocytes and mononuclear cells (MNCs). We measured levels of sIL-6R using a sensitive and specific enzyme-linked immunosorbent assay. Synovial cells, chondrocytes and MNCs were cultured, and the supernatants were also measured for sIL-6R. SF levels of sIL-6R in RA were significantly higher than those in OA. SF levels of sIL-6R significantly correlated with SF levels of IL-6 in RA. The serum level of sIL-6R was approximately 3-fold higher than the SF level of sIL-6R sIL-6R protein was not detected in the supernatants of synovial cells and chondrocytes. As compared to the SF levels of sIL-6R, a small amount of sIL-6R protein was produced by SF MNCs. The above findings suggest that increased amounts of sIL-6R form IL-6-sIL-6R complexes which mediate IL-6 function in RA joints and that SF sIL-6R protein might be not only produced in affected joints, but also supplied from the serum.

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Monocyte activation in early onset rheumatoid arthritis.

Cited by 35 publications

References 37 publications

Elevated cytokine messenger RNA levels in the peripheral blood of patients with rheumatoid arthritis suggest different degrees of myeloid cell activation

Elevated cytokine messenger RNA levels in the peripheral blood of patients with rheumatoid arthritis suggest different degrees of myeloid cell activation

Synovial interleukin‐1 receptor antagonist and interleukin‐1 balance in rheumatoid arthritis

Synovial fluid and serum levels of soluble interleukin-6 receptor in patients with rheumatoid arthritis

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