title: Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen.
abstract: Viral respiratory infections can predispose to the development of asthma by mechanisms that are presently undetermined. Using a murine model of respiratory syncytial virus (RSV) infection, acute infection is associated with airway hyperresponsiveness as well as enhanced responses to subsequent sensitization to allergen. We demonstrate that acute viral infection results in increased airway responsiveness to inhaled methacholine and pulmonary neutrophilic and eosinophilic inflammation. This response is associated with predominant production of Th-1-type cytokines in peribronchial lymph node cells in vitro. Mice sensitized to ovalbumin via the airways after RSV infection developed increased airway responsiveness to methacholine and pulmonary eosinophilic and neutrophilic inflammation, associated with the predominant production of Th-2-type cytokines. Treatment of the mice with anti-IL-5 antibody abolished airway hyperresponsiveness and eosinophilic but not neutrophilic inflammation in both acutely infected mice and mice sensitized after infection. We conclude that RSV infection results in airway hyperresponsiveness in the acute phase and leads to changes in immune function that can enhance the effects of airway sensitization to antigen after infection. In both situations, airway hyperresponsiveness is closely associated with pulmonary eosinophilic inflammation. This model provides a means for further analyzing the influence of viral respiratory infections on airway sensitization and the development of altered airway responsiveness.
authors.affiliation: Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
authors.forename: J
authors.initials: J
authors.lastname: Schwarze
authors.forename: E
authors.initials: E
authors.lastname: Hamelmann
authors.forename: K L
authors.initials: KL
authors.lastname: Bradley
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: E W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000485:Allergens; D000818:Animals; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology*; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000485:Allergens; D016085:Bronchoconstrictor Agents; D016207:Cytokines; D015848:Interleukin-5; D016210:Methacholine Chloride; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin