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Rheumatology Advance Access originally published online on October 17, 2003
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Rheumatology 2004; 43: 39-42
© British Society for Rheumatology 2003

Basic Science

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

J.-H. Gong, R. Yan1, J. D. Waterfield1 and I. Clark-Lewis{dagger}

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

Correspondence to: J. D. Waterfield, Faculty of Dentistry, 2199 Wesbrook Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

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

Notes

{dagger}This paper is dedicated to Dr I. Clark-Lewis, whose untimely death has saddened his many friends and collaborators in the scientific community.


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