Involvement of macrophage migration inhibitory factor in the evolution of rat adjuvant arthritis

Arthritis Rheum. 1998 May;41(5):910-7. doi: 10.1002/1529-0131(199805)41:5<910::AID-ART19>3.0.CO;2-E.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Arthritis, Experimental / metabolism*
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / prevention & control
  • Blotting, Western
  • Cell Count / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Edema / drug therapy
  • Enzyme-Linked Immunosorbent Assay
  • Immunohistochemistry
  • Macrophage Migration-Inhibitory Factors / immunology
  • Macrophage Migration-Inhibitory Factors / metabolism*
  • Macrophages / metabolism
  • Male
  • Neutralization Tests
  • Rats
  • Rats, Sprague-Dawley
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology


  • Antibodies, Monoclonal
  • Macrophage Migration-Inhibitory Factors