Involvement of macrophage migration inhibitory factor in the evolution of rat adjuvant arthritis.
OBJECTIVE: Recent studies have established an essential role for macrophage migration inhibitory factor (MIF) in T cell and macrophage activation, both of which are characteristics of rat adjuvant arthritis. This study investigated the role of MIF in early adjuvant arthritis. METHODS: MIF was detected in rat synovium by immunohistochemistry and enzyme-linked immunosorbent assay using specific monoclonal antibodies (MAb). Anti-MIF MAb treatment was administered, and the effects on clinical aspects of adjuvant arthritis were assessed. RESULTS: MIF was absent from normal rat synovium prior to adjuvant injection, but was detectable on day 4 after injection (6 days before the onset of clinical disease) and was colocalized with ED-1+ macrophages throughout the evolution of the disease. Levels of MIF were increased in established adjuvant arthritis sera, and adjuvant arthritis synovial macrophages released MIF at a mean +/- SEM concentration of 607.9 +/- 201.5 pg/ml. Anti-MIF treatment led to profound, dose-dependent inhibition of the adjuvant arthritis clinical score, paw swelling, and synovial lavage leukocyte numbers (P < 0.001), and also resulted in reduced synovial macrophage and T cell accumulation. CONCLUSION: These findings demonstrate an important role for MIF in the evolution of rat adjuvant arthritis.[1]References
- Involvement of macrophage migration inhibitory factor in the evolution of rat adjuvant arthritis. Leech, M., Metz, C., Santos, L., Peng, T., Holdsworth, S.R., Bucala, R., Morand, E.F. Arthritis Rheum. (1998) [Pubmed]
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