Aerosol inoculation with a sub-lethal influenza virus leads to exacerbated morbidity and pulmonary disease pathogenesis.

Abstract

A mouse model has been extensively used to investigate disease intervention approaches and correlates of immunity following influenza virus infection. The majority of studies examining cross-reactive and protective immune responses have used intranasal (IN) virus inoculation; however, infectious aerosols are a common means of transmitting influenza in the human population. In this study, IN and aerosol routes of inoculation were compared and end-points of immunity and disease pathogenesis were evaluated in mice using mouse-adapted H3N2 A/Aichi/2/68 (x31). Aerosol inoculation with sub-lethal x31 levels caused more robust infection, which was characterized by enhanced morbidity, mortality, pulmonary cell infiltration, and inflammation, compared to IN-inoculated mice, as well as higher levels of IL-6 expression in the lung. Treatment with IL-6-blocking antibodies reduced pulmonary infiltrates and lung pathology in aerosol-inoculated mice. This study shows that aerosol inoculation results in a distinctive host response and disease outcome compared to IN inoculation, and suggests a possible role for IL-6 in lung pathogenesis.

• Authors: Jennifer Humberd Smith, Tamas Nagy, Jamie Barber, Paula Brooks, S Mark Tompkins, Ralph A Tripp
• Journal: Viral immunology (Viral Immunol) Vol. 24 Issue 2 Pg. 131-42 (Apr 2011) ISSN: 1557-8976 [Electronic] United States
• PMID: 21449723 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Aerosols

Topics

• Administration, Inhalation
• Administration, Intranasal
• Aerosols
• Animals
• Female
• Influenza A Virus, H3N2 Subtype (immunology, pathogenicity)
• Lung (immunology, pathology)
• Lung Diseases (immunology, pathology, virology)
• Mice
• Mice, Inbred BALB C
• Orthomyxoviridae Infections (immunology, pathology, virology)