title: Exacerbation of influenzavirus pneumonia by intranasal administration of surfactant in a mouse model.
abstract: Although surfactant-secreting type II alveolar cells have been shown to be damaged during influenzavirus pneumonia, little is known about the effects of surfactant replacement therapy. We have developed a mouse influenza model, in which viral infection can be localized to the upper respiratory tract or to both the upper and lower respiratory tract depending on the volume (rather than infectious dose) of intranasal inocula of influenzavirus. In this model, only mice infected with a large inocula die with massive infection in the lung. Using this model, we unexpectedly found that intranasal administration of surfactant dramatically exacerbated influenzavirus infection causing fatal disease even in mice inoculated with a small inocula. This exacerbation resulted from enhancement of intrabronchial and intraalveolar spread of virus, as confirmed by immunohistochemical detection of viral antigen in lungs. Assuming this experimental model in mice recapitulates naturally occurring disease in humans, extreme caution is warranted in surfactant-replacement treatment of influenzavirus pneumonia in humans.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwasaki
authors.forename: S
authors.initials: S
authors.lastname: Tamura
authors.forename: T
authors.initials: T
authors.lastname: Kumasaka
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Hasegawa
authors.forename: H
authors.initials: H
authors.lastname: Asanuma
authors.forename: S
authors.initials: S
authors.lastname: Aizawa
authors.forename: R
authors.initials: R
authors.lastname: Yanagihara
authors.forename: T
authors.initials: T
authors.lastname: Kurata
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002642:Chick Embryo; D003643:Death; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation; D009980:Influenza A virus; D007251:Influenza, Human / Q000473:pathology / Q000503:physiopathology* / Q000635:transmission; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000473:pathology; D011024:Pneumonia, Viral / Q000473:pathology / Q000503:physiopathology*; D013501:Surface-Active Agents / Q000494:pharmacology*; D016019:Survival Analysis
chemical_list: D013501:Surface-Active Agents