title: Intratracheal administration of influenza virus is superior to intranasal administration as a model of acute lung injury.
abstract: Infection of mice with human or murine adapted influenza A viruses results in a severe pneumonia. However, the results of studies from different laboratories show surprising variability, even in genetically similar strains. Differences in inoculum size related to the route of viral delivery (intranasal vs. intratracheal) might explain some of this variability. To test this hypothesis, mice were infected intranasally or intratracheally with different doses of influenza A virus (A/WSN/33 [H1N1]). Daily weights, a requirement for euthanasia, viral load in the lungs and brains, inflammatory cytokines, wet-to-dry ratio, total protein and histopathology of the infected mice were examined. With all doses of influenza tested, intranasal delivery resulted in less severe lung injury, as well as smaller and more variable viral loads in the lungs when compared with intratracheal delivery. Virus was not detected in the brain following either method of delivery. It is concluded that compared to intranasal infection, intratracheal infection with influenza A virus is a more reliable method to deliver virus to the lungs.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Luisa
authors.initials: L
authors.lastname: Morales-Nebreda
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Monica
authors.initials: M
authors.lastname: Chi
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Emilia
authors.initials: E
authors.lastname: Lecuona
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Navdeep S
authors.initials: NS
authors.lastname: Chandel
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dada
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Karen
authors.initials: K
authors.lastname: Ridge
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Saul
authors.initials: S
authors.lastname: Soberanes
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Recep
authors.initials: R
authors.lastname: Nigdelioglu
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Jacob I
authors.initials: JI
authors.lastname: Sznajder
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Gökhan M
authors.initials: GM
authors.lastname: Mutlu
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: G R Scott
authors.initials: GR
authors.lastname: Budinger
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States. Electronic address: k-radigan@northwestern.edu.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Radigan
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology* / Q000821:virology*; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000821:virology; D004195:Disease Models, Animal; D006651:Histocytochemistry; D006801:Humans; D009980:Influenza A virus / Q000254:growth & development* / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D008810:Mice, Inbred C57BL; D009296:Nasal Cavity / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000473:pathology* / Q000821:virology*; D014132:Trachea / Q000821:virology; D019562:Viral Load
keywords: Influenza A infection; Inoculation; Intranasal; Intratracheal; Lung injury; Mice