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

Abstract

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. Conclusion. The evidence suggests that PK 11195 may be the prototype of a new class of anti-inflammatory agents.