Open AccessInvolvement of macrophage migration inhibitory factor in the evolution of rat adjuvant arthritis
Author(s) -
Leech Michelle,
Metz Christine,
Santos Leilani,
Peng Tina,
Holdsworth Stephen R.,
Bucala Richard,
Morand Eric F.
Publication year - 1998
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(199805)41:5<910::aid-art19>3.0.co;2-e
Subject(s) - macrophage migration inhibitory factor , arthritis , adjuvant , medicine , immunology , macrophage , immunohistochemistry , monoclonal antibody , antibody , pathology , cytokine , biology , in vitro , biochemistry
Abstract 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.