title: Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung.
abstract: 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.
authors.affiliation: Department of Medicine/Immunobiology, The University of Vermont, Burlington, Vermont, USA.
authors.forename: O
authors.initials: O
authors.lastname: Dienz
authors.forename: J G
authors.initials: JG
authors.lastname: Rud
authors.forename: S M
authors.initials: SM
authors.lastname: Eaton
authors.forename: P A
authors.initials: PA
authors.lastname: Lanthier
authors.forename: E
authors.initials: E
authors.lastname: Burg
authors.forename: A
authors.initials: A
authors.lastname: Drew
authors.forename: J
authors.initials: J
authors.lastname: Bunn
authors.forename: B T
authors.initials: BT
authors.lastname: Suratt
authors.forename: L
authors.initials: L
authors.lastname: Haynes
authors.forename: M
authors.initials: M
authors.lastname: Rincon
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000235:genetics; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D018375:Neutrophil Activation / Q000235:genetics; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019562:Viral Load / Q000235:genetics
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6