Role of interleukin-1, tumor necrosis factor α, and interleukin-6 in cartilage proteoglycan metabolism and destruction : effect of in situ blocking in murine antigen- and zymosan-induced arthritis
In: Arthritis and rheumatism, Jg. 38 (1995), Heft 2, S. 164-172
Online
academicJournal
- print, 36 ref
Zugriff:
Objective. To determine the involvement of interleukin-1 (IL-1), tumor necrosis factor (TNF), and IL-6 in the cartilage pathology of murine antigen-induced arthritis (AIA) and zymosan-induced arthritis (ZIA). Methods. Arthritis was induced by intraarticular injection of zymosan in naive mice or by subcutaneous injection of methylated bovine serum albumin in sensitized animals. Mini-osmotic pumps releasing human recombinant IL-1 receptor antagonist (IL-1ra) protein were implanted intraperitoneally 2 days before arthritis induction, and neutralizing antibodies directed against murine U-1α, IL-1β, TNFα, or IL-6 were administered 1 day before. Proteoglycan (PG) synthesis and degradation were assessed in patellar cartilage. Results. Murine IL-1α and IL-1β injected intraarticularly at doses of 0.1-100 ng suppressed chondrocyte PG synthesis. The highest dose of TNF tested (100 ng) decreased PG synthesis marginally. In contrast, the maximum dose of IL-6 (1 μg) stimulated PG synthesis 2 days after injection. Treatment of AIA with neutralizing monoclonal antibodies against either TNFα or IL-6 did not reduce either the PG degradation or the suppression of its synthesis. However, treatment with anti-IL-1 (α+β) polyclonal antibodies totally prevented PG suppression, although the initial breakdown of PG was unaffected. This effect was confirmed when IL-1ra was administered in high doses. Moreover, treatment of ZIA with anti-IL-1 (α+β), but not with anti-TNF, resulted in normal PG synthesis, confirming the key role played by IL-1 in the inhibition of PG synthesis. Treatment of AIA with anti-IL-1 did not affect inflammation during the acute phase, but a significant reduction of ongoing inflammation was noted at day 7, and there was a marked reduction in the loss of cartilage PG. Conclusion. The suppression of PG synthesis in both ZIA and AIA in mice is due to the combined local action of IL-1 (α+β), and neither IL-6 nor TNF is involved. Moreover, the normalization of PG synthesis brought about by blocking of IL-1 ameliorates the cartilage damage associated with AIA.
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Role of interleukin-1, tumor necrosis factor α, and interleukin-6 in cartilage proteoglycan metabolism and destruction : effect of in situ blocking in murine antigen- and zymosan-induced arthritis
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Autor/in / Beteiligte Person: | VAN DE LOO, F. A. J ; JOOSTEN, L. A. B ; VAN LENT, P. L. E. M ; ARNTZ, O. J ; VAN DEN BERG, W. B |
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Zeitschrift: | Arthritis and rheumatism, Jg. 38 (1995), Heft 2, S. 164-172 |
Veröffentlichung: | Hoboken , NJ: Wiley, 1995 |
Medientyp: | academicJournal |
Umfang: | print, 36 ref |
ISSN: | 0004-3591 (print) |
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