The peripheral benzodiazepine receptor ligand PK 11195 inhibits arthritis in the MRL-lpr mouse model.
OBJECTIVE
Mice of the MRL-lpr strain develop a severe autoimmune arthritic condition when primed with complete Freund's adjuvant. The pathology is similar to that seen in human rheumatoid arthritis. We investigated whether PK 11195, a powerful ligand for peripheral benzodiazepine receptors, would have preventative or therapeutic effects in this model.


METHODS
MRL-lpr mice were primed with complete Freund's adjuvant at 13-14 weeks of age. Daily PK 11195 injections were started on the same day as priming to test for preventative effects. Daily PK 11195 injections were started 10 days after priming to test therapeutic effects.


RESULTS
PK 11195 showed both preventative and therapeutic effects. At 1 mg/kg/day, it inhibited disease onset. At 3 mg/kg/day, it inhibited established disease progression.


CONCLUSIONS
The evidence suggests that PK 11195 may be the prototype of a new class of anti-inflammatory agents.
Waterfield
J D
JD
Department of Oral Biological Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
McGeer
E G
EG
McGeer
P L
PL
D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines / Q000627:therapeutic use*; D008024:Ligands; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr
D018501:Antirheumatic Agents; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines; D008024:Ligands; C037850:PK 11195