Therapeutic efficacy of L‐kynurenine on Collagen Induced Arthritis (CIA) in mice

The evolution of CIA, a chronic inflammatory disease, is associated with both B‐ and T lymphocytes responses with the production of anti‐collagen antibodies and Th1/Th2 cytokines. The tryptophan catabolites of kynurenine pathway are known as predominant immunomodulators with potential to treat autoimmune diseases. Here we examined the preventive effects of L‐kynurenine on the progression of arthritis and inflammatory response in mice. Arthritis was induced in DBA/1J mice by subcutaneous immunization with bovine type II collagen on day 0 and 21. After the onset of arthritis, mice were randomly grouped (n=10) and intraperitonially injected with kynurenine (50, 100 and 200mg/kg/day) or phosphate buffered saline alone for 15days. Arthritis severity was monitored by scoring system, and hindlimb paw and ankle swelling were measured using calipers. Serum anti‐collagen IgG and cytokines levels were determined using ELISA. Kynurenine significantly reduced arthritis severity, serum levels of total and anti‐collagen IgG, IL‐6, IL‐12, IL‐23, and TNF‐α, while IL‐10 and IL‐15 levels markedly increased in a dose dependent manner. However, the serum levels of IgG2a, IgG2b, IL‐12 and IL‐23 tended to increase towards the end of the experiment at higher concentration. The results suggest that regular administration of 100mg/kg kynurenine would be the effective therapeutic approach to suppress the severity of arthritis.