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Lipid mediators of inflammation and resolution in individuals with tuberculosis and tuberculosis-diabetes
Prostaglandins and Other Lipid Mediators
Individuals with concurrent tuberculosis (TB) and Type 2 diabetes (DM) have a higher risk of adverse outcomes. To better understand potential immunological differences, we utilized a comprehensive panel to characterize pro-inflammatory and pro-resolving (i.e., mediators involved in the resolution of inflammation) lipid mediators in individuals with TB and TB-DM. A nested cross-sectional study of 40 individuals (20 newly diagnosed DM and 20 without DM) was conducted within a cohort of individuals with active drug-susceptible treatment-naïve pulmonary TB. Lipid mediators were quantified in serum samples through lipid mediator profiling. We conducted correlation-based analysis of these mediators. Overall, the arachidonic acid-derived leukotriene and prostaglandin families were the most abundant pro-inflammatory lipid mediators, while lipoxins and maresins families were the most abundant pro-resolving lipid mediators in individuals with TB and TB-DM. Individuals with TB-DM had increased correlations and connectivity with both pro-inflammatory and pro-resolving lipid mediators compared to those with TB alone. We identified the most abundant lipid mediator metabolomes in circulation among individuals with TB and TB-DM; in addition, our data shows a substantial number of significant correlations between both pro-inflammatory and pro-resolving lipid mediators in individuals with TB-DM, delineating a molecular balance that potentially defines this comorbidity.
Shivakoti R, Dalli J, Kadam D, Gaikwad S, Barthwal M, Colas RA, Mazzacuva F, Lokhande R, Dharmshale S, Bharadwaj R, Kagal A, Pradhan N, Deshmukh S, Atre S, Sahasrabudhe T, Kakrani A, Kulkarni V, Raskar S, Suryavanshi N, Chon S, Gupte A, Gupta A, Gupte N, Arriaga MB, Fukutani KF, Andrade BB, Golub JE, Mave V. Lipid mediators of inflammation and resolution in individuals with tuberculosis and tuberculosis-diabetes. Prostaglandins Other Lipid Mediat. 2019 Nov 11;147:106398. doi: 10.1016/j.prostaglandins.2019.106398. [Epub ahead of print]. PMID: 31726221; PMCID: PMC7067657.