Published ahead of print on July 8, 2004, doi:10.1164/rccm.200311-1488OC
Am. J. Respir. Crit. Care Med., Volume 170, Number 8, October 2004, 851-856
A more recent version of this article appeared on October 15, 2004
Submitted on November 12, 2003
Accepted on June 30, 2004
Is Interleukin-13 Critical in Maintaining Airway Hyperresponsiveness in Allergen Challenged Mice?
Richard Leigh1, Russ Ellis1, Jennifer Wattie1, Debra D Donaldson2, and Mark D Inman1*
1 Firestone Institute for Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada,
2 Wyeth Pharmaceuticals Inc., Wyeth Research, Cambridge, MA, USA
* To whom correspondence should be addressed. E-mail: inmanma{at}mcmaster.ca.
Interleukin (IL)-13 is regarded as being a central effector in the pathophysiology of airway hyperresponsiveness. We have described a mouse model in which chronic allergen exposure results in sustained airway hyperresponsiveness and aspects of airway remodeling, and here sought to demonstrate that this component of airway hyperresponsiveness is independent of biologically active IL-13. Sensitized mice were subjected to either brief or chronic periods of allergen exposure and studied 24 hours after brief or 4 weeks after chronic allergen inhalation. A soluble murine anti-IL-13 receptor fusion protein, that specifically binds to and neutralizes IL-13, was given daily during the 4 days prior to outcome measurements in both protocols. Outcomes included airway responses to intravenous methacholine, bronchoalveolar lavage cell counts and airway morphometry. Compared to saline control, brief allergen challenge resulted in airway hyperresponsiveness, which was prevented by anti-IL-13 treatment. Chronic allergen challenge resulted in sustained airway hyperresponsiveness and indices of airway remodeling; IL-13 blockade failed to reverse this sustained airway hyperresponsiveness. These results confirm that IL-13 is critical for the development of airway hyperresponsiveness associated with brief allergen exposure, but is not necessary to maintain the sustained airway hyperresponsiveness associated with airway remodeling.
Key words: Allergic disease, asthma, bronchial hyperreactivity, airway inflammation
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