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Circulating tumour necrosis factor-α bioactivity in rheumatoid arthritis patients treated with infliximab: link to clinical response
Our objective was to clarify the heterogeneity in response to infliximab treatment in rheumatoid arthritis (RA); to this end, a bioassay was designed to explore the contribution of circulating tumour necrosis factor (TNF)-α bioactivity and its possible link to response. The bioassay is based on the...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2005
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1064892/ https://www.ncbi.nlm.nih.gov/pubmed/15642135 http://dx.doi.org/10.1186/ar1465 |
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author | Marotte, Hubert Maslinski, Wlodzimierz Miossec, Pierre |
author_facet | Marotte, Hubert Maslinski, Wlodzimierz Miossec, Pierre |
author_sort | Marotte, Hubert |
collection | PubMed |
description | Our objective was to clarify the heterogeneity in response to infliximab treatment in rheumatoid arthritis (RA); to this end, a bioassay was designed to explore the contribution of circulating tumour necrosis factor (TNF)-α bioactivity and its possible link to response. The bioassay is based on the induction of IL-6 and osteoprotegerin (OPG) production by synoviocytes in response to TNF-α. RA synoviocytes were cultured with TNF-α (5 ng/ml) and 42 RA plasma samples collected just before starting therapy. Levels of IL-6 and OPG were measured in supernatants. In 20 of the patients, plasma samples collected before and 4 hours after the first and the ninth infusions were tested in the same way. Plasma concentrations of TNF-α and p55 and p75 soluble receptors were measured using ELISA. TNF-α induced IL-6 and OPG production by synoviocytes, which was further increased with patient plasma dilutions and inhibited by infliximab. With plasma samples obtained before the first infusion, the IL-6-induced production was greater in patients with a good clinical response than in the poor responders (44.4 ± 23.3 ng/ml versus 27.4 ± 20.9 ng/ml; P = 0.05). This high circulating TNF-α bioactivity was strongly inhibited with the first infliximab infusion. The difference between IL-6 levels induced with plasma samples obtained before and 4 hours after the first infusion was greater in patients with a good clinical response (40.0 ± 23.7 ng/ml versus 3.4 ± 10.0 ng/ml; P = 0.001). Similar findings were obtained for OPG production (7.0 ± 6.2 ng/ml versus 0.0 ± 3.0 ng/ml; P < 0.05). Levels of circulating TNF-α bioactivity were predictive of clinical response to TNF-α inhibition, confirming a key role for TNF-α in these RA patients. |
format | Text |
id | pubmed-1064892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-10648922005-03-12 Circulating tumour necrosis factor-α bioactivity in rheumatoid arthritis patients treated with infliximab: link to clinical response Marotte, Hubert Maslinski, Wlodzimierz Miossec, Pierre Arthritis Res Ther Research Article Our objective was to clarify the heterogeneity in response to infliximab treatment in rheumatoid arthritis (RA); to this end, a bioassay was designed to explore the contribution of circulating tumour necrosis factor (TNF)-α bioactivity and its possible link to response. The bioassay is based on the induction of IL-6 and osteoprotegerin (OPG) production by synoviocytes in response to TNF-α. RA synoviocytes were cultured with TNF-α (5 ng/ml) and 42 RA plasma samples collected just before starting therapy. Levels of IL-6 and OPG were measured in supernatants. In 20 of the patients, plasma samples collected before and 4 hours after the first and the ninth infusions were tested in the same way. Plasma concentrations of TNF-α and p55 and p75 soluble receptors were measured using ELISA. TNF-α induced IL-6 and OPG production by synoviocytes, which was further increased with patient plasma dilutions and inhibited by infliximab. With plasma samples obtained before the first infusion, the IL-6-induced production was greater in patients with a good clinical response than in the poor responders (44.4 ± 23.3 ng/ml versus 27.4 ± 20.9 ng/ml; P = 0.05). This high circulating TNF-α bioactivity was strongly inhibited with the first infliximab infusion. The difference between IL-6 levels induced with plasma samples obtained before and 4 hours after the first infusion was greater in patients with a good clinical response (40.0 ± 23.7 ng/ml versus 3.4 ± 10.0 ng/ml; P = 0.001). Similar findings were obtained for OPG production (7.0 ± 6.2 ng/ml versus 0.0 ± 3.0 ng/ml; P < 0.05). Levels of circulating TNF-α bioactivity were predictive of clinical response to TNF-α inhibition, confirming a key role for TNF-α in these RA patients. BioMed Central 2005 2004-12-01 /pmc/articles/PMC1064892/ /pubmed/15642135 http://dx.doi.org/10.1186/ar1465 Text en Copyright © 2004 Marotte et al., licensee BioMed Central Ltd. |
spellingShingle | Research Article Marotte, Hubert Maslinski, Wlodzimierz Miossec, Pierre Circulating tumour necrosis factor-α bioactivity in rheumatoid arthritis patients treated with infliximab: link to clinical response |
title | Circulating tumour necrosis factor-α bioactivity in rheumatoid arthritis patients treated with infliximab: link to clinical response |
title_full | Circulating tumour necrosis factor-α bioactivity in rheumatoid arthritis patients treated with infliximab: link to clinical response |
title_fullStr | Circulating tumour necrosis factor-α bioactivity in rheumatoid arthritis patients treated with infliximab: link to clinical response |
title_full_unstemmed | Circulating tumour necrosis factor-α bioactivity in rheumatoid arthritis patients treated with infliximab: link to clinical response |
title_short | Circulating tumour necrosis factor-α bioactivity in rheumatoid arthritis patients treated with infliximab: link to clinical response |
title_sort | circulating tumour necrosis factor-α bioactivity in rheumatoid arthritis patients treated with infliximab: link to clinical response |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1064892/ https://www.ncbi.nlm.nih.gov/pubmed/15642135 http://dx.doi.org/10.1186/ar1465 |
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