Respiratory syncytial virus infection provokes airway remodelling in allergen-exposed mice in absence of prior allergen sensitization

Clin Exp Allergy. 2008 Jun;38(6):1016-24. doi: 10.1111/j.1365-2222.2008.02974.x.

Abstract

Background: The mechanisms underlying exacerbation of asthma induced by respiratory syncytial virus (RSV) infection have been extensively studied in human and animal models. However, most of these studies focused on acute inflammation and little is known of its long-term consequences on remodelling of the airway tissue.

Objective: The aim of the study was to use a murine model of prolonged allergen-induced airway inflammation to investigate the effect of RSV infection on allergic airway inflammation and tissue remodelling.

Methods: We subjected mice to RSV infection before or during the chronic phase of airway challenges with OVA and compared parameters of airway inflammation and remodelling at the end-point of the prolonged allergen-induced airway inflammation protocol.

Results: RSV infection did not affect the severity of airway inflammation in any of the groups studied. However, RSV infection provoked airway remodelling in non-sensitized, allergen-challenged mice that did not otherwise develop any of the features of allergic airways disease. Increased collagen synthesis in the lung and thickening of the bronchial basal membrane was observed in non-sensitized allergen-challenged mice only after prior RSV infection. In addition, fibroblast growth factor (FGF)-2 but not TGF-beta(1) was increased in this group following RSV infection.

Conclusion: Our data show for the first time that RSV infection can prime the lung of mice that are not previously systemically sensitized, to develop airway remodelling in response to allergen upon sole exposure via the airways. Moreover, our results implicate RSV-induced FGF-2 in the remodelling process in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alum Compounds / administration & dosage
  • Analysis of Variance
  • Animals
  • Asthma / immunology
  • Asthma / pathology*
  • Asthma / virology
  • Bronchoalveolar Lavage Fluid / immunology
  • Collagen / metabolism
  • Cytokines / metabolism
  • Extracellular Matrix / metabolism
  • Female
  • Fibroblast Growth Factor 2 / metabolism
  • Immunohistochemistry
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology*
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / metabolism
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Viruses*
  • Statistics, Nonparametric
  • Transforming Growth Factor beta / metabolism

Substances

  • Alum Compounds
  • Cytokines
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 2
  • aluminum sulfate
  • Ovalbumin
  • Collagen