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. Issue 8 (1st August 2002)

• Record Type: Journal Article
• Authors: Chevrel, G; Garnero, P; Miossec, P
• Is Part Of: Annals of the rheumatic diseases. Volume 61:Issue 8(2002)
• Page Start: 730
• Page End: 733
• Publication Date: 2002-08-01
• Subjects: tumour necrosis factor α -- synoviocytes -- interleukin 6; DC, dendritic cells -- ELISA, enzyme linked immunosorbent assay -- IL, interleukin -- MIP-3α, macrophage inflammatory protein-3α -- PBMC, peripheral blood mononuclear cells -- P1CP, type 1 procollagen carboxy-terminal propeptide -- PHA, phytohaemagglutinin -- PMA, phorbol 12-myristate 13-acetate -- RA, rheumatoid arthritis -- sR, soluble receptors -- sTNFR, TNFα soluble receptors -- TNFα, tumour necrosis factor α; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.61.8.730
• Languages: English
• ISSNs: 0003-4967

Abstract

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 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.