title: Respiratory syncytial virus infection does not increase allergen-induced type 2 cytokine production, yet increases airway hyperresponsiveness in mice.
abstract: 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.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2582, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Peebles
authors.forename: J R
authors.initials: JR
authors.lastname: Sheller
authors.forename: R D
authors.initials: RD
authors.lastname: Collins
authors.forename: A K
authors.initials: AK
authors.lastname: Jarzecka
authors.forename: D B
authors.initials: DB
authors.lastname: Mitchell
authors.forename: R A
authors.initials: RA
authors.lastname: Parker
authors.forename: B S
authors.initials: BS
authors.lastname: Graham
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology*; D007114:Immunization; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses; D013047:Specific Pathogen-Free Organisms
chemical_list: D000485:Allergens; D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D012333:RNA, Messenger; D015847:Interleukin-4; D010047:Ovalbumin