|
||
By


From the * Biomedical Research Centre and Department of Biochemistry and Molecular Biology, and An antagonist of human monocyte chemoattractant protein (MCP)-1, which consists of MCP-1(9-76), had previously been characterized and shown to inhibit MCP-1 activity in vitro. To
test the hypothesis that, by inhibiting endogenous MCP-1, the antagonist has antiinflammatory activity in vivo, we examined its effect in the MRL-lpr mouse model of arthritis. This strain
spontaneously develops a chronic inflammatory arthritis that is similar to human rheumatoid
arthritis. Daily injection of the antagonist, MCP-1(9-76), prevented the onset of arthritis as
monitored by measuring joint swelling and by histopathological evaluation of the joints. In
contrast, controls treated with native MCP-1 had enhanced arthritis symptoms, indicating that
the inhibitory effect is specific to the antagonist. In experiments where the antagonist was given
only after the disease had already developed, there was a marked reduction in symptoms and
histopathology, although individuals varied in the magnitude of the response. The mechanism
of inhibition of disease is not known, although the results suggest that it could be more complex than the competitive inhibition of ligand binding that is observed in vitro. The demonstration of the beneficial effects of an MCP-1 antagonist in arthritis suggests that chemokine receptor antagonists could have therapeutic application in inflammatory diseases.
Department of Oral Biology and Department of Microbiology, University of British Columbia,
Vancouver, British Columbia V6T 1Z3, Canada
This article has been cited by other articles:
| TABLE OF CONTENTS |
|