Respiratory syncytial virus infection does not increase allergen-induced type 2 cytokine production, yet increases airway hyperresponsiveness in mice

J Med Virol. 2001 Feb;63(2):178-88.


Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined murine models of allergen-sensitization and RSV infection to explore the interaction of allergic and virus-induced airway inflammation and its impact on airway hyperresponsiveness (AHR). We found that RSV infection during ova-sensitization (OVA/RSV) increased and prolonged AHR compared to mice only RSV-infected (RSV) or ova-sensitized (OVA). AHR is known to be associated with an increase in Type 2 cytokines (IL-4, IL-5, and IL-13) in allergen-sensitized mice. Therefore, we hypothesized that RSV-induced enhancement of AHR was a result of potentiating the Type 2 cytokine profile promoted by ova-sensitization. Surprisingly, we found that Type 2 cytokines induced by ova-sensitization were not increased by RSV infection despite the increase in AHR, and in some cases were diminished. RNAse protection assay revealed no difference in IL-4 and IL-5 mRNA levels between the OVA and OVA/RSV groups, and IL-13 mRNA was significantly decreased in the OVA/RSV mice compared to the OVA group. Flow cytometric analysis of Type 2 cytokines demonstrated the same frequency of IL-4 and IL-5 production in lung-derived T lymphocytes from the OVA/RSV and OVA groups. Direct cytokine ELISA measurements of lung supernatant showed the level of IL-13 was significantly decreased in the OVA/RSV group compared to OVA mice, while there was no difference in either IL-4 or IL-5 between these two groups. These data indicate that the enhanced and prolonged AHR caused by the interaction of allergic airway inflammation and virus-induced immune responses is a complex process that can not be explained simply by augmented production of Type 2 cytokines.

Publication types

  • Comparative Study

MeSH terms

  • Allergens / immunology*
  • Animals
  • Cytokines / analysis
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Hypersensitivity / immunology*
  • Immunization
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Lung / immunology
  • Lymphocytes / immunology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • RNA, Messenger / analysis
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Viruses*
  • Specific Pathogen-Free Organisms


  • Allergens
  • Cytokines
  • Interleukin-13
  • Interleukin-5
  • RNA, Messenger
  • Interleukin-4
  • Ovalbumin