Respiratory syncytial virus-induced airway hyperresponsiveness is independent of IL-13 compared with that induced by allergen

Jung Won Park, Christian Taube, Eun Seok Yang, Anthony Joetham, Annette Balhorn, Katsuyuki Takeda, Nobuaki Miyahara, Azzeddine Dakhama, Debra D. Donaldson, Erwin W. Gelfand

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Abstract

Background: IL-13 is a central mediator of allergen-induced airway hyperresponsiveness (AHR), but its role in respiratory syncytial virus (RSV)-induced AHR is not defined. The combination of allergen exposure and RSV infection is known to increase AHR and lung inflammation, but whether IL-13 regulates this increase is similarly not known. Objective: Our objective was to determine the role of RSV infection and IL-13 on airway responsiveness and lung inflammation on sensitized and challenged mice. Methods: Using a murine model of RSV infection and allergen exposure, we examined the role of IL-13 in the development of AHR and lung inflammation in IL-13 knockout mice, as well as using a potent IL-13 inhibitor (IL-13i). Mice were sensitized and challenged to allergen, and 6 days after the last challenge, they were infected with RSV. IL-13 was inhibited using an IL-13 receptor α2-human IgG fusion protein. AHR to inhaled methacholine was measured 6 days after infection, as was bronchoalveolar lavage fluid and lung inflammatory and cytokine responses. Results: RSV-induced AHR was unaffected by the IL-13i, despite prevention of goblet cell hyperplasia. Similar results were seen in IL-13-deficient mice. In sensitized and challenged mice, RSV infection significantly increased AHR, and after IL-13i treatment, AHR was significantly reduced, but to the levels seen in RSV-infected mice alone. Conclusions: These results indicate that despite some similarities, the mechanisms leading to AHR induced by RSV are different from those that follow allergen sensitization and challenge. Because IL-13 inhibition is effective in preventing the increases in AHR and mucus production in sensitized and challenged mice infected with RSV, IL-13i could play an important role in preventing the consequences of viral infection in patients with allergic asthma.

Original languageEnglish
Pages (from-to)1078-1087
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume112
Issue number6
DOIs
Publication statusPublished - Dec 2003
Externally publishedYes

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Keywords

  • Airway hyperresponsiveness
  • IL-13
  • Respiratory syncytial virus

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Park, J. W., Taube, C., Yang, E. S., Joetham, A., Balhorn, A., Takeda, K., Miyahara, N., Dakhama, A., Donaldson, D. D., & Gelfand, E. W. (2003). Respiratory syncytial virus-induced airway hyperresponsiveness is independent of IL-13 compared with that induced by allergen. Journal of Allergy and Clinical Immunology, 112(6), 1078-1087. https://doi.org/10.1016/j.jaci.2003.08.046