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Addition of interleukin 1 (IL1) and IL17 soluble receptors to a tumour necrosis factor alpha soluble receptor more effectively reduces the production of IL6 and macrophage inhibitory protein-3alpha and increases that of collagen in an in vitro model of rheumatoid synoviocyte activation.

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Affiliations

  • 1. Department of Immunology, Hôpital E Herriot, 69437 Lyon Cedex 03, France.
      Authors
    • Chevrel G 1
    (1 author)

Annals of the Rheumatic Diseases, 01 Aug 2002, 61(8):730-733
https://doi.org/10.1136/ard.61.8.730 PMID: 12117682 PMCID: PMC1754206

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Abstract 

Objectives

To evaluate the usefulness of combination treatment with cytokine inhibitors.

Methods

A simplified model was set up to evaluate the effect of tumour necrosis factor alpha (TNFalpha) soluble receptors (sTNFR) used alone and in combination with soluble interleukin 1 receptor (sIL1R) and sIL17R on the production of markers of inflammation (IL6), of migration of dendritic cells (macrophage inhibitory protein-3alpha (MIP-3alpha)), and of matrix synthesis (C-propeptide of type 1 collagen (P1CP)). Synoviocytes were stimulated with supernatants of activated peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA). Soluble receptors (sR) were preincubated at 1 gammag/ml alone or in combination with the supernatants before addition to RA synoviocytes. IL6, MIP-3alpha, and P1CP production was measured by enzyme linked immunosorbent assay (ELISA) in 48 hour synoviocyte supernatants.

Results

IL6 production decreased by 16% with sTNFR alone compared with no sTNFR (p<0.001) and by 41% with the combination of the three sR (p<0.001). MIP-3alpha production decreased by 77% with sTNFR alone compared with no sTNFR (p<0.001) and by 98% with the combination of the three sR (p<0.001). In the presence of sTNFR alone, P1CP production increased by 25% compared with no sR (p<0.01). The combination of the three sR increased P1CP production by 48% (p<0.01).

Conclusion

The effect of sTNFR on IL6, MIP-3alpha, and P1CP production by RA synoviocytes stimulated by activated PBMC supernatants was further enhanced when combined with sIL1R and sIL17R.

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Logo of annrheumdLink to Publisher's site
Ann Rheum Dis. 2002 Aug; 61(8): 730–733.
PMCID: PMC1754206
PMID: 12117682

Addition of interleukin 1 (IL1) and IL17 soluble receptors to a tumour necrosis factor α soluble receptor more effectively reduces the production of IL6 and macrophage inhibitory protein-3α and increases that of collagen in an in vitro model of rheumatoid synoviocyte activation

G Chevrel, P Garnero, and P Miossec
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Abstract

Methods: A simplified model was set up to evaluate the effect of tumour necrosis factor α (TNFα) soluble receptors (sTNFR) used alone and in combination with soluble interleukin 1 receptor (sIL1R) and sIL17R on the production of markers of inflammation (IL6), of migration of dendritic cells (macrophage inhibitory protein-3α (MIP-3α)), and of matrix synthesis (C-propeptide of type 1 collagen (P1CP)). Synoviocytes were stimulated with supernatants of activated peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA). Soluble receptors (sR) were preincubated at 1 γg/ml alone or in combination with the supernatants before addition to RA synoviocytes. IL6, MIP-3α, and P1CP production was measured by enzyme linked immunosorbent assay (ELISA) in 48 hour synoviocyte supernatants.

Results: IL6 production decreased by 16% with sTNFR alone compared with no sTNFR (p<0.001) and by 41% with the combination of the three sR (p<0.001). MIP-3α production decreased by 77% with sTNFR alone compared with no sTNFR (p<0.001) and by 98% with the combination of the three sR (p<0.001). In the presence of sTNFR alone, P1CP production increased by 25% compared with no sR (p<0.01). The combination of the three sR increased P1CP production by 48% (p<0.01).

Conclusion: The effect of sTNFR on IL6, MIP-3α, and P1CP production by RA synoviocytes stimulated by activated PBMC supernatants was further enhanced when combined with sIL1R and sIL17R.

Full Text

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Figures and Tables

An external file that holds a picture, illustration, etc. Object name is 01513.f1.jpg

Dose-response curve of sTNFR, sIL1R, and sIL17R alone or in combination on IL6 production. Supernatants (SN) of activated RA PBMC were incubated with synoviocytes and increasing concentrations of sTNFR sIL1R, and sIL17R ranging from 0.1 to 100 µg/ml, used alone or in combination. IL6 levels were measured by ELISA in 48 hour supernatants. Results represent the mean of the effect of supernatants from two different patients with RA on the same RA synoviocytes.

An external file that holds a picture, illustration, etc. Object name is 01513.f2.jpg

Effect of sTNFR, sIL1R, and sIL17R alone or in combination on IL6, MIP-3α, and P1CP production by RA synoviocytes stimulated with supernatants of activated PBMC from patients with RA. (A) IL6 production; (B) MIP-3α production; (C) P1CP production. Synoviocytes were cultured with supernatants (SN) of activated PBMC from patients with RA (n=20: IL6 ; n=14: MIP-3α and P1CP) and 1 µg/ml of sTNFR, sIL1R, sIL17R, alone or in combination. IL6 (ng/ml), MIP-3α (pg/ml), and P1CP production (ng/ml) were measured by ELISA in 48 hour synoviocyte supernatants. sR-treated SN versus non-treated SN: *p<0.001, **p<0.01.

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

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Read article at publisher's site: https://doi.org/10.1136/ard.61.8.730

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