Anti-IL-12 and anti-TNF antibodies synergistically suppress the progression of murine collagen-induced arthritis.
The co-ordinate role of the Th1 cytokine IL-12 and the proinflammatory cytokine TNF in arthritis was explored using the DBA/1 mouse model, collagen-induced arthritis (CIA). In this study, mice with established arthritis were treated with anti-IL-12 and/or anti-TNF antibodies for 10 days from the ons...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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1999
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| _version_ | 1797090901506392064 |
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| author | Butler, D Malfait, A Maini, R Brennan, F Feldmann, M |
| author_facet | Butler, D Malfait, A Maini, R Brennan, F Feldmann, M |
| author_sort | Butler, D |
| collection | OXFORD |
| description | The co-ordinate role of the Th1 cytokine IL-12 and the proinflammatory cytokine TNF in arthritis was explored using the DBA/1 mouse model, collagen-induced arthritis (CIA). In this study, mice with established arthritis were treated with anti-IL-12 and/or anti-TNF antibodies for 10 days from the onset of disease. Clinical assessment showed that the combined antibody treatment ameliorated disease severity to a greater extent than anti-TNF alone. Supporting these observations, histological analysis revealed that there was a reduced joint damage in the mice that received combined anti-IL-12 and anti-TNF treatment, compared to the other treatment groups. Anti-IL-12 had no statistically significant effect on the clinical outcome of disease. The combination of anti-IL-12 and anti-TNF treatment was found to reduce collagen type II (CII)-specific lymph node cell IFN-gamma production and proliferation, as well as decrease the anti-CII IgG2a:IgG1 ratio more effectively than either treatment alone. When the antibodies were added to synovial cells from arthritic mice and bone marrow macrophages in vitro, anti-TNF diminished IL-12 production, but anti-IL-12 had no effect on TNF production. These data suggest that, through the partial regulation of IL-12, TNF modulates the immune response in arthritis, as well as the inflammatory response. The synergistic action of anti-TNF and anti-IL-12 on CIA may provide a new therapeutic approach for treating rheumatoid arthritis. |
| first_indexed | 2024-03-07T03:25:19Z |
| format | Journal article |
| id | oxford-uuid:b8d6289c-3571-437e-9f3b-da833bc6f38e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:25:19Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:b8d6289c-3571-437e-9f3b-da833bc6f38e2022-03-27T04:58:40ZAnti-IL-12 and anti-TNF antibodies synergistically suppress the progression of murine collagen-induced arthritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b8d6289c-3571-437e-9f3b-da833bc6f38eEnglishSymplectic Elements at Oxford1999Butler, DMalfait, AMaini, RBrennan, FFeldmann, MThe co-ordinate role of the Th1 cytokine IL-12 and the proinflammatory cytokine TNF in arthritis was explored using the DBA/1 mouse model, collagen-induced arthritis (CIA). In this study, mice with established arthritis were treated with anti-IL-12 and/or anti-TNF antibodies for 10 days from the onset of disease. Clinical assessment showed that the combined antibody treatment ameliorated disease severity to a greater extent than anti-TNF alone. Supporting these observations, histological analysis revealed that there was a reduced joint damage in the mice that received combined anti-IL-12 and anti-TNF treatment, compared to the other treatment groups. Anti-IL-12 had no statistically significant effect on the clinical outcome of disease. The combination of anti-IL-12 and anti-TNF treatment was found to reduce collagen type II (CII)-specific lymph node cell IFN-gamma production and proliferation, as well as decrease the anti-CII IgG2a:IgG1 ratio more effectively than either treatment alone. When the antibodies were added to synovial cells from arthritic mice and bone marrow macrophages in vitro, anti-TNF diminished IL-12 production, but anti-IL-12 had no effect on TNF production. These data suggest that, through the partial regulation of IL-12, TNF modulates the immune response in arthritis, as well as the inflammatory response. The synergistic action of anti-TNF and anti-IL-12 on CIA may provide a new therapeutic approach for treating rheumatoid arthritis. |
| spellingShingle | Butler, D Malfait, A Maini, R Brennan, F Feldmann, M Anti-IL-12 and anti-TNF antibodies synergistically suppress the progression of murine collagen-induced arthritis. |
| title | Anti-IL-12 and anti-TNF antibodies synergistically suppress the progression of murine collagen-induced arthritis. |
| title_full | Anti-IL-12 and anti-TNF antibodies synergistically suppress the progression of murine collagen-induced arthritis. |
| title_fullStr | Anti-IL-12 and anti-TNF antibodies synergistically suppress the progression of murine collagen-induced arthritis. |
| title_full_unstemmed | Anti-IL-12 and anti-TNF antibodies synergistically suppress the progression of murine collagen-induced arthritis. |
| title_short | Anti-IL-12 and anti-TNF antibodies synergistically suppress the progression of murine collagen-induced arthritis. |
| title_sort | anti il 12 and anti tnf antibodies synergistically suppress the progression of murine collagen induced arthritis |
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