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Rheumatology Advance Access published online on October 17, 2003

Rheumatology, doi:10.1093/rheumatology/keg459
Rheumatology © British Society for Rheumatology 2003; all rights reserved
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© 2003 © 2003 British Society for Rheumatology

Original Papers

Post-onset inhibition of murine arthritis using combined chemokine antagonist therapy

J.-H. Gong 1, R. Yan 2, J. D. Waterfield 2*, and I. Clark-Lewis 1

1 Biomedical Research Centre and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
2 Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada

Received 4 December 2002 ; accepted 5 June 2003

Abstract

Objective. To investigate the effect of targeting the chemotaxis of monocytes and polymorphonuclear monocytes (PMNs) in situ in MRL-Faslpr arthritis.

Methods. MRL-Faslpr mice were injected intradermally with complete Freund’s adjuvant and cellular infiltration into the joint was monitored. Once clinical disease developed, the animals received one of three treatments: MCP-1(9-76); MCP-1(9-76) plus Gro-{alpha}(8-73); or control peptide, MCP-1 Ala. The bimalleolar ankle width was measured for 11 days and histological examination of the joints was then assessed.

Results. Cellular infiltration started after the onset of ankle swelling, and increased progressively. The incidence of swelling and the histopathology was reduced after day 6 of treatment in the MCP-1(9-76)-treated mice. Mice treated with the two antagonists MCP-1(9-76) and Gro-{alpha}(8-73) displayed a further significant reduction in disease parameters.

Conclusion. Treatment after disease onset with chemotactic antagonists for monocytes and PMNs significantly alleviated both the swelling and the histopathology seen in arthritis, suggesting that chemokine antagonists are an effective anti-inflammatory therapy.

Key words: Arthritis, Chemokines, Antagonists.
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