Kynurenine-to-tryptophan ratio and inflammatory cytokines in people living with HIV from a metabolomic perspective

Abstract Metabolic dysregulation and infections have a bidirectional relationship; metabolic dysregulation increase susceptibility to infections, while infections exacerbate metabolic dysregulation. Coinfection of HIV and tuberculosis (TB) leads to persistent immune activation, depleting the body’s energy and nutrient reserves and weakening immune defenses. This study aims to evaluate the kynurenine/tryptophan (K/T) ratio as a biomarker of metabolic dysregulation and its correlation with pro-inflammatory cytokines IL-6 and IL-17 in HIV-infected individuals with and without active or latent TB. A total of 72 subjects aged ≥ 18 years, consisting of 24 HIV-infected without TB, 23 with latent TB infection (LTBI), and 25 with active TB, were enrolled. Serum levels of kynurenine and tryptophan were measured using enzyme-linked immunosorbent assay (ELISA), and IL-6 and IL-17 cytokines were analyzed via flow cytometric bead array (CBA). The mean K/T ratio was significantly elevated in the HIV-active TB group (0.032) compared to HIV without TB (0.015) and HIV-LTBI (0.015) groups ( p = 0.005). No significant differences were observed in cytokine levels among groups; however, IL-17 tended to be lower in the HIV without TB group and higher in the HIV-LTBI group compared to the active TB group. No correlation was found between the K/T ratio and levels of IL-6 or IL-17. The kynurenine/tryptophan ratio effectively differentiates metabolic disturbances in HIV patients with active TB but shows no correlation with T lymphocyte activation markers IL-6 and IL-17. Further studies are necessary to elucidate the mechanistic pathways and clinical relevance for patient management.