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

Jungwon 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 - 2003 Jan 1

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Respiratory Syncytial Viruses
Interleukin-13
Allergens
Respiratory Syncytial Virus Infections
Pneumonia
Interleukin-13 Receptors
Goblet Cells
Methacholine Chloride
Bronchoalveolar Lavage Fluid
Virus Diseases
Mucus
Knockout Mice
Hyperplasia
Asthma
Immunoglobulin G

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Park, Jungwon ; Taube, Christian ; Yang, Eun Seok ; Joetham, Anthony ; Balhorn, Annette ; Takeda, Katsuyuki ; Miyahara, Nobuaki ; Dakhama, Azzeddine ; Donaldson, Debra D. ; Gelfand, Erwin W. / Respiratory syncytial virus-induced airway hyperresponsiveness is independent of IL-13 compared with that induced by allergen. In: Journal of Allergy and Clinical Immunology. 2003 ; Vol. 112, No. 6. pp. 1078-1087.
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title = "Respiratory syncytial virus-induced airway hyperresponsiveness is independent of IL-13 compared with that induced by allergen",
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.",
author = "Jungwon Park and Christian Taube and Yang, {Eun Seok} and Anthony Joetham and Annette Balhorn and Katsuyuki Takeda and Nobuaki Miyahara and Azzeddine Dakhama and Donaldson, {Debra D.} and Gelfand, {Erwin W.}",
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Park, J, Taube, C, Yang, ES, Joetham, A, Balhorn, A, Takeda, K, Miyahara, N, Dakhama, A, Donaldson, DD & Gelfand, EW 2003, 'Respiratory syncytial virus-induced airway hyperresponsiveness is independent of IL-13 compared with that induced by allergen', Journal of Allergy and Clinical Immunology, vol. 112, no. 6, pp. 1078-1087. https://doi.org/10.1016/j.jaci.2003.08.046

Respiratory syncytial virus-induced airway hyperresponsiveness is independent of IL-13 compared with that induced by allergen. / Park, Jungwon; Taube, Christian; Yang, Eun Seok; Joetham, Anthony; Balhorn, Annette; Takeda, Katsuyuki; Miyahara, Nobuaki; Dakhama, Azzeddine; Donaldson, Debra D.; Gelfand, Erwin W.

In: Journal of Allergy and Clinical Immunology, Vol. 112, No. 6, 01.01.2003, p. 1078-1087.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Respiratory syncytial virus-induced airway hyperresponsiveness is independent of IL-13 compared with that induced by allergen

AU - Park, Jungwon

AU - Taube, Christian

AU - Yang, Eun Seok

AU - Joetham, Anthony

AU - Balhorn, Annette

AU - Takeda, Katsuyuki

AU - Miyahara, Nobuaki

AU - Dakhama, Azzeddine

AU - Donaldson, Debra D.

AU - Gelfand, Erwin W.

PY - 2003/1/1

Y1 - 2003/1/1

N2 - 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.

AB - 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.

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