Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung

Mucosal Immunol. 2012 May;5(3):258-66. doi: 10.1038/mi.2012.2. Epub 2012 Feb 1.


Influenza virus infection is considered a major worldwide public health problem. Seasonal infections with the most common influenza virus strains (e.g., H1N1) can usually be resolved, but they still cause a high rate of mortality. The factors that influence the outcome of the infection remain unclear. Here, we show that deficiency of interleukin (IL)-6 or IL-6 receptor is sufficient for normally sublethal doses of H1N1 influenza A virus to cause death in mice. IL-6 is necessary for resolution of influenza infection by protecting neutrophils from virus-induced death in the lung and by promoting neutrophil-mediated viral clearance. Loss of IL-6 results in persistence of the influenza virus in the lung leading to pronounced lung damage and, ultimately, death. Thus, we demonstrate that IL-6 is a vital innate immune cytokine in providing protection against influenza A infection. Genetic or environmental factors that impair IL-6 production or signaling could increase mortality to influenza virus infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Death / genetics
  • Cell Death / immunology
  • Cells, Cultured
  • Cytoprotection / genetics
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H1N1 Subtype / pathogenicity
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Lung / immunology*
  • Lung / pathology
  • Lung / virology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Neutrophil Activation / genetics
  • Neutrophils / immunology*
  • Neutrophils / pathology
  • Neutrophils / virology
  • Orthomyxoviridae Infections / immunology*
  • Receptors, Interleukin-6 / genetics
  • Receptors, Interleukin-6 / immunology
  • Receptors, Interleukin-6 / metabolism
  • Viral Load / genetics


  • Interleukin-6
  • Receptors, Interleukin-6