IL-1 alpha beta blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-alpha blockade only ameliorates joint inflammation
| Autor: | L A, Joosten, M M, Helsen, T, Saxne, F A, van De Loo, D, Heinegard, W B, van Den Berg |
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| Rok vydání: | 1999 |
| Předmět: |
Cartilage
Articular Male Extracellular Matrix Proteins Tumor Necrosis Factor-alpha Immune Sera Tarsus Animal Arthritis Experimental Bone and Bones Peptide Fragments Receptors Tumor Necrosis Factor Radiography Epitopes Mice Antigens CD Mice Inbred DBA Receptors Tumor Necrosis Factor Type I Animals Matrilin Proteins Cattle Joints Collagen Oligopeptides Injections Intraperitoneal Glycoproteins Interleukin-1 |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 163(9) |
| ISSN: | 0022-1767 |
| Popis: | Anti-TNF-alpha treatment of rheumatoid arthritis patients markedly suppresses inflammatory disease activity, but so far no tissue-protective effects have been reported. In contrast, blockade of IL-1 in rheumatoid arthritis patients, by an IL-1 receptor antagonist, was only moderately effective in suppressing inflammatory symptoms but appeared to reduce the rate of progression of joint destruction. We therefore used an established collagen II murine arthritis model (collagen-induced arthritis(CIA)) to study effects on joint structures of neutralization of either TNF-alpha or IL-1. Both soluble TNF binding protein and anti-IL-1 treatment ameliorated disease activity when applied shortly after onset of CIA. Serum analysis revealed that early anti-TNF-alpha treatment of CIA did not decrease the process in the cartilage, as indicated by the elevated COMP levels. In contrast, anti-IL-1 treatment of established CIA normalized COMP levels, apparently alleviating the process in the tissue. Histology of knee and ankle joints corroborated the finding and showed that cartilage and joint destruction was significantly decreased after anti-IL-1 treatment but was hardly affected by anti-TNF-alpha treatment. Radiographic analysis of knee and ankle joints revealed that bone erosions were prevented by anti-IL-1 treatment, whereas the anti-TNF-alpha-treated animals exhibited changes comparable to the controls. In line with these findings, metalloproteinase activity, visualized by VDIPEN production, was almost absent throughout the cartilage layers in anti-IL-1-treated animals, whereas massive VDIPEN appearance was found in control and sTNFbp-treated mice. These results indicate that blocking of IL-1 is a cartilage- and bone-protective therapy in destructive arthritis, whereas the TNF-alpha antagonist has little effect on tissue destruction. |
| Databáze: | OpenAIRE |
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