Macrophage migration inhibitory factor in rheumatoid arthritis: clinical correlations.
OBJECTIVE
Cytokines play an important role in the pathology of rheumatoid arthritis (RA). Macrophage migration inhibitory factor (MIF) is a cytokine with a broad spectrum of actions, including induction of monocyte tumour necrosis factor alpha (TNF-alpha). Evidence of the expression and proinflammatory activity of MIF has recently been demonstrated in RA synovium and in animal models of RA. We wished to assess the relationship between MIF expression in synovium and clinical disease.


METHODS
Computer-assisted analysis of the cytokine content of arthroscopically obtained biopsies of RA synovium, using paired samples from eight patients with active and inactive/treated disease, was compared with documented clinical parameters.


RESULTS
Synovial MIF immunostaining correlated strongly with disease activity as measured by CRP concentration. Reductions in clinical disease parameters, including CRP, tender and swollen joint counts, were accompanied by significant reductions in synovial MIF. Synovial TNF-alpha, transforming growth factor beta (TGF-beta) and interleukin (IL) 10 also showed a significant reduction in association with reduced disease activity, while IL-1 beta and IL-1 receptor agonist did not.


CONCLUSIONS
The correlation of synovial MIF with disease activity corroborates existing evidence of the role of this cytokine in RA. The demonstration that only MIF and TNF-alpha show significant variation in synovial cytokine content with clinical remission suggests that MIF is an important member of the cytokine hierarchy in RA.
Morand
E F
EF
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Melbourne, South Australia, Australia.
Leech
M
M
Weedon
H
H
Metz
C
C
Bucala
R
R
Smith
M D
MD
D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002097:C-Reactive Protein / Q000032:analysis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D007596:Joints / Q000473:pathology / Q000503:physiopathology; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D018715:Microscopy, Video; D015846:Monokines / Q000378:metabolism; D010147:Pain Measurement; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
D018501:Antirheumatic Agents; D008263:Macrophage Migration-Inhibitory Factors; D015846:Monokines; D002097:C-Reactive Protein