A platelet activating factor receptor antagonist prevents the development of chronic arthritis in mice.
OBJECTIVE
To examine the effect of treatment with the platelet activating factor (PAF) receptor antagonist BN 50730 on the clinical and morphological evolution of collagen induced arthritis in mice.


METHODS
Mice with collagen induced arthritis were treated with BN 50730 (0.3, 1, 3 mg/kg) or vehicle (0.1% Tween-20 in saline) once a day, from 3 days before the induction of the arthritis to 70 days after. Disease evolution was followed daily by inspection of inflammatory signs and measurement of the knee joint diameter on Days 0, 40, and 70. At the end of the treatment period, the morphological evaluation of the synovial membrane, the immunodetection of fibronectin, and the content of cartilage proteoglycans were studied.


RESULTS
On Day 40, mice receiving the highest dose of BN 50730 (3 mg/kg) showed a reduction in the knee joint diameter in comparison with untreated (2.1 +/- 0.2 vs 2.8 +/- 0.4 mm, p < 0.01). On Day 70, animals receiving 1 and 3 mg/kg had a normal knee diameter, while it remained enlarged in the untreated ones. In BN 50730 treated mice (3 mg/kg) we also observed a significant reduction of the inflammation score (0.1 +/- 0.1 vs 2.5 +/- 0.2 in the untreated) and deposition of fibronectin. Depletion of cartilage proteoglycans was also reversed with BN 50730.


CONCLUSIONS
The beneficial effects in this model of joint injury after administration of the PAF antagonist BN 50730 suggest that PAF could be implicated in the pathogenesis of chronic arthritis.
Palacios
I
I
Inflammation Research Laboratory, Rheumatology Division, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Miguélez
R
R
Sánchez-Pernaute
O
O
Gutierrez
S
S
Egido
J
J
Herrero-Beaumont
G
G
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000517:prevention & control*; D001381:Azepines / Q000627:therapeutic use*; D003094:Collagen; D004195:Disease Models, Animal; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D007150:Immunohistochemistry; D007596:Joints / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D058924:Thienopyridines; D014230:Triazoles / Q000627:therapeutic use*
D001381:Azepines; D005353:Fibronectins; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D058924:Thienopyridines; D014230:Triazoles; C039351:platelet activating factor receptor; C066686:BN 50730; D003094:Collagen