Lipidomic profiling of influenza infection identifies mediators that induce and resolve inflammation

Cell. 2013 Jul 3;154(1):213-27. doi: 10.1016/j.cell.2013.05.052.


Bioactive lipid mediators play a crucial role in the induction and resolution of inflammation. To elucidate their involvement during influenza infection, liquid chromatography/mass spectrometry lipidomic profiling of 141 lipid species was performed on a mouse influenza model using two viruses of significantly different pathogenicity. Infection by the low-pathogenicity strain X31/H3N2 induced a proinflammatory response followed by a distinct anti-inflammatory response; infection by the high-pathogenicity strain PR8/H1N1 resulted in overlapping pro- and anti-inflammatory states. Integration of the large-scale lipid measurements with targeted gene expression data demonstrated that 5-lipoxygenase metabolites correlated with the pathogenic phase of the infection, whereas 12/15-lipoxygenase metabolites were associated with the resolution phase. Hydroxylated linoleic acid, specifically the ratio of 13- to 9-hydroxyoctadecadienoic acid, was identified as a potential biomarker for immune status during an active infection. Importantly, some of the findings from the animal model were recapitulated in studies of human nasopharyngeal lavages obtained during the 2009-2011 influenza seasons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / metabolism
  • Cytokines / immunology
  • Disease Models, Animal
  • Eicosanoids / immunology
  • Eicosanoids / isolation & purification*
  • Fatty Acids, Unsaturated / immunology
  • Fatty Acids, Unsaturated / isolation & purification*
  • Humans
  • Inflammation Mediators / analysis
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza A Virus, H3N2 Subtype / physiology*
  • Influenza, Human / immunology*
  • Lipids / analysis*
  • Metabolic Networks and Pathways
  • Mice
  • Nasal Lavage Fluid / immunology
  • Orthomyxoviridae Infections / immunology*
  • Transcriptome


  • Cytokines
  • Eicosanoids
  • Fatty Acids, Unsaturated
  • Inflammation Mediators
  • Lipids
  • hydroxyoctadecadienoic acid
  • Arachidonate 5-Lipoxygenase