Abstract
Kynurenic acid (KYNA) has recognized anti-inflammatory and immunosuppressive properties. Previous studies demonstrated that KYNA reduces TNF-α, S100A12, S100A8/9, and α-defensin production while increasing tumor necrosis factor-stimulated gene-6 protein (TSG-6) levels in rheumatoid arthritis. This study evaluated a synthetic KYNA analog's effects on TNF-α, S100A8/9, S100A12, α-defensin, and interleukin-17 (IL-17) production and TSG-6 expression in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Peripheral blood mononuclear cells from 54 AS and 38 PsA patients and 11 healthy controls were stimulated with heat-inactivated Staphylococcus aureus (SA1). Parallel cultures were pretreated with the KYNA analog. Cytokine and alarmin concentrations were measured by ELISA. SA1 stimulation increased TNF-α, TSG-6, calprotectin, and α-defensin production, with minimal effects on S100A12 and none on IL-17. The KYNA analog significantly reduced SA1-induced TNF-α, calprotectin, and α-defensin levels and enhanced TSG-6 production, without affecting S100A12 or IL-17. Notably, the TNF-α inhibitory and TSG-6 stimulatory effects were inversely correlated. Conclusion: KYNA analogs may exert anti-inflammatory effects via TSG-6 upregulation, contributing to the suppression of key cytokines. These findings support further exploration of KYNA derivatives as therapeutic options in immune-mediated diseases including AS and PsA.