The failure of interleukin-10-deficient mice to develop airway hyperresponsiveness is overcome by respiratory syncytial virus infection in allergen-sensitized/challenged mice

Mika J. Mäkelä, Arihiko Kanehiro, Azzeddine Dakhama, Larry Borish, Anthony Joetham, Ralph Tripp, Larry Anderson, Erwin W. Gelfand

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Interleukin-10-deficient mice develop a robust pulmonary inflammatory response but no airway hyperresponsiveness (AHR) to inhaled methacholine (MCh) following allergen sensitization and challenge. In the present study, we investigated the effect of respiratory syncytial virus (RSV) infection on AHR and pulmonary inflammation in allergic IL-10-/- mice. Unlike littermate control mice, RSV-infected or ovalbumin (OVA)-sensitized/challenged IL-10-/- mice failed to develop significant AHR. In contrast, sensitized /challenged IL-10-/- mice infected with RSV did develop AHR accompanied by increased eosinophil numbers, both in bronchoalveolar lavage (BAL) and pulmonary tissue, and mucin production in airway epithelium. The cytokine profile in OVA-sensitized/challenged IL-10-/- mice was skewed toward a Th1 response but after RSV infection, this response was more of a Th2 type, with increased IL-5 levels in the BAL. Studies with an RSV mutant that lacks the G and SH genes showed equal enhancement of the AHR response as the parental wild-type strain, indicating that G protein is not essential to this response. These data suggest that RSV infection can overcome the failure of development of AHR in allergic IL-10-/- mice.

Original languageEnglish
Pages (from-to)824-831
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume165
Issue number6
DOIs
Publication statusPublished - Mar 15 2002

Keywords

  • Allergen sensitization
  • Eosinophilia
  • IL-10
  • Lung function
  • Respiratory syncytial virus

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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