Is interleukin-13 critical in maintaining airway hyperresponsiveness in allergen-challenged mice?
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 before the day of outcome measurements in both protocols. Outcome measurements included airway responses to intravenous methacholine, bronchoalveolar lavage fluid cell counts, and airway morphometry. Compared with the 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.
Leigh
Richard
R
Firestone Institute for Respiratory Health, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.
Ellis
Russ
R
Wattie
Jennifer
J
Donaldson
Debra D
DD
Inman
Mark D
MD
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D005260:Female; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000502:physiology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000276:immunology; D053660:Receptors, Interleukin-13
D000485:Allergens; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D010047:Ovalbumin