Metabolic pathways of lung inflammation revealed by high-resolution metabolomics (HRM) of H1N1 influenza virus infection in mice.

摘要: Influenza is a significant health concern worldwide. Viral infection induces local and systemic activation of the immune system causing attendant changes in metabolism. High-resolution metabolomics (HRM) uses advanced mass spectrometry computational methods to measure thousands metabolites inclusive most metabolic pathways. We used HRM identify pathways clusters association related inflammatory cytokines lungs mice with H1N1 influenza virus infection. Infected showed progressive weight loss, decreased lung function, severe inflammation elevated [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ] increased oxidative stress via cysteine oxidation. prominent effects on tryptophan other amino acids, widespread including purines, pyrimidines, fatty glycerophospholipids. A metabolome-wide study (MWAS) aforementioned was determine relationship responses during This cytokine-MWAS (cMWAS) that associations consisted distinct shared 396 highly correlated cytokines. Strong negative selected glycosphingolipid, linoleate, IFN-γ contrasted strong positive glycosphingolipid bile acid IL-1β, TNF-α, IL-10. Anti-inflammatory cytokine IL-10 had vitamin D, purine, E The detailed interactions indicate targeted interventions may be useful life-threatening crises acute inflammation.