Macrophage infiltration into the rat knee detected by MRI in a model of antigen-induced arthritis.
Three-dimensional (3D) MR images were obtained from the knees of rats in a model of antigen-induced arthritis, elicited by the intraarticular administration of methylated bovine serum albumin (mBSA) to previously immunized rats. Superparamagnetic particles of iron oxide (SPIO) were administered i.v. 24 hr before each imaging session. Starting 4 days postantigen injection, images from arthritic knees exhibited distinctive signal attenuation in the synovium. This signal attenuation was significantly smaller in knees from animals treated with dexamethasone, a glucocorticosteroid, and completely absent in contralateral knees that had been challenged with vehicle. A significant negative correlation was found between the MRI signal intensity in the synovium and the histologically determined iron content in macrophages located in the same region. These results suggest the feasibility of detecting macrophage infiltration into the knee synovium in this model of antigen-induced arthritis by labeling the cells with SPIO. This readout could provide an early marker of disease progression, before more aggressive changes like cartilage and bone erosion take place. Monitoring early changes associated with arthritis can have an impact in preclinical studies by shortening the duration of the experimental period and by facilitating the investigation of novel immunomodulatory therapies acting on macrophages. Also, the approach can be potentially adapted to clinical studies.
Beckmann
Nicolau
N
Central Technologies, Novartis Institutes for Biomedical Research, Basel, Switzerland. nicolau.beckmann@pharma.novartis.com
Falk
Regina
R
Zurbrügg
Stefan
S
Dawson
Janet
J
Engelhardt
Petra
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D002452:Cell Count; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005290:Ferric Compounds; D006614:Hindlimb / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D051381:Rats; D011917:Rats, Inbred Lew; D012710:Serum Albumin, Bovine
D000893:Anti-Inflammatory Agents; D005290:Ferric Compounds; C000499:ferric oxide; D012710:Serum Albumin, Bovine; D003907:Dexamethasone