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.


CONCLUSIONS
These findings demonstrate an important role for MIF in the evolution of rat adjuvant arthritis.
Leech
M
M
Monash Medical Centre, Clayton, Melbourne, Australia.
Metz
C
C
Santos
L
L
Peng
T
T
Holdsworth
S R
SR
Bucala
R
R
Morand
E F
EF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015153:Blotting, Western; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009500:Neutralization Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D008263:Macrophage Migration-Inhibitory Factors