(Scientific Session) Synovium Production of Kynurenine in Arthritic Knee Joints: Implications for Treating Comorbid Pain and Depression in Osteoarthritis

Background and/or Objectives: Osteoarthritis (OA) is a leading cause of pain, disability, and healthcare utilization in the US. Approximately 40% of patients with chronic OA develop depression. Our previous work demonstrated the synovial fluid of osteoarthritic joints contains elevated levels of kynurenine (KYN). KYN is produced through the metabolism of tryptophan (TRP) by the enzyme indoleamine-2,3-dioxygenase (IDO). IDO activity is upregulated by the same inflammatory cytokines responsible for OA. It is unknown whether KYN is produced within an OA joint or if it is produced systemically and crosses through the synovium. To answer this question, we performed TRP/KYN pathway manipulation on OA cartilage and synovium. The results of this study provide insight into the suitability of KYN as a potential therapeutic target for pain and depression in OA.

Design: Cross-sectional

Setting: Laboratory

Participants: 20 patients undergoing total knee arthroplasty for end-stage osteoarthritis.

Interventions: not applicable.

Main Outcome Measures: Cartilage and synovium kynurenine and kynurenic acid production

Results: Our results show that the addition of TRP significantly increased KYN production in synovium samples but not in cartilage samples. Moreover, the addition of TRP significantly increased KYNA production in both the synovium and cartilage samples but the increase was significantly greater in the synovium.

Conclusions: Our data suggest synovium is the primary independent producer of KYN in the setting of OA. Moreover, these data demonstrate that KYN production, responsible for pain and depression, can be significantly increased in the setting of TRP but not necessarily decreased in the setting of the IDO antagonist 1-L-MT.