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


CONCLUSIONS
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.
Gong
J-H
JH
Biomedical Research Centre and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Yan
R
R
Waterfield
J D
JD
Clark-Lewis
I
I
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D018932:Chemokine CCL2 / Q000627:therapeutic use; D054360:Chemokine CXCL1; D018925:Chemokines / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D002630:Chemotactic Factors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use; D007596:Joints / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D023421:Models, Animal; D009000:Monocytes / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D010446:Peptide Fragments / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; C475896:CXCL1 protein, Bos taurus; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D018925:Chemokines; D002630:Chemotactic Factors; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; C106929:monocyte chemoattractant protein 1 (9-76)