Various therapeutics can lead to drug-induced interstitial lung disease (DIILD) either via direct toxicity or from secondary effects due to immune activation. Mortality rates in DIILD have been reported as upwards of 50% and individuals who recover often have long-term effects, including lung fibrosis. Currently, patients are diagnosed by high-resolution computed tomography scans however, there is a need for a non-invasive method of diagnosis that can differentiate individuals with DILD from other pulmonary diseases while limiting radiation exposure.
Dr. Yuchen Sun and colleagues sought to find new biomarkers that are specific to DIILD. In their metabolomic screening, they identified five kynurenine-derived peaks that were significantly increased in DIILD patients compared to recovered patients. Due to their initial observations, the researchers looked further into the kynurenine pathway. Quinolinic acid, kynurenine, and the kynurenine/tryptophan ratio were increased in the serum of DIILD patients but not in individuals who had recovered. Furthermore, using these markers distinguished DIILD from other pneumonia/lung diseases. Suggesting that these KP metabolites can be used to detect DIILD. These findings need to be confirmed in larger cohorts and different demographics.
Since immune activation can lead to DIILD they looked further into the molecular mechanisms that may underlie the kynurenine pathway activation. Consistent with other studies, they found that IDO1 expression is induced by inflammatory mediators, such as interferon-γ, both in macrophages and lung endothelial cells. Kynurenine and quinolinic acid were increased in macrophages following interferon stimulation but only kynurenine was increased in lung endothelial cells. Highlighting the need for further research into the cell types and mechanisms involved in kynurenine pathway dysregulation in DIILD.