The peripheral benzodiazepine receptor ligand PK 11195 inhibits arthritis in the MRL-lpr mouse model

Objective. Mice of the MRL-1pr strain develop a severe autoimmune arthritic condition when primed with complete Freund's adjuvant. The pathology is si milar to that seen in human rheumatoid arthritis. We investigated whether P K 11195, a powerful ligand for peripheral benzodiazepine receptors, would h ave preventative or therapeutic effects in this model. Methods. MRL-1pr 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 pri ming to test for preventative effects. Daily PK 11195 injections were start ed 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 establish ed disease progression. Conclusion. The evidence suggests that PK 11195 may be the prototype of a n ew class of anti-inflammatory agents.