title: The role of IL-13 in established allergic airway disease.
abstract: The effectiveness of targeting IL-13 in models where airway hyperresponsiveness (AHR) and airway inflammation have already been established is not well-described. We investigated the effects of blocking IL-13 on the early and late phase airway responses and the development of AHR in previously sensitized and challenged mice. BALB/cByJ mice were sensitized (days 1 and 14) and challenged (days 28-30) with OVA. Six weeks later (day 72), previously sensitized/challenged mice were challenged with a single OVA aerosol and the early and late phase response and development of AHR were determined. Specific in vivo blockade of IL-13 was attained after i.p. injection of a soluble IL-13Ralpha2-IgG fusion protein (sIL-13Ralpha2Fc) on days 71-72 for the early and late responses and on days 71-73 for the development of AHR. sIL-13Ralpha2Fc administration inhibited the late, but not early, phase response and the OVA challenge-induced changes in lung resistance and dynamic compliance; as well, sIL-13Ralpha2Fc administration decreased bronchoalveolar lavage eosinophilia and mucus hypersecretion following the secondary challenge protocols. These results demonstrate that targeting IL-13 alone regulates airway responses when administrated to mice with established allergic airway disease. These data identify the importance of IL-13 in the development of allergen-induced altered airway responsiveness following airway challenge, even when administered before rechallenge of mice in which allergic disease had been previously established.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.forename: Catherine
authors.initials: C
authors.lastname: Duez
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Cui
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Yeong-Ho
authors.initials: YH
authors.lastname: Rha
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Annette
authors.initials: A
authors.lastname: Balhorn
authors.forename: Debra D
authors.initials: DD
authors.lastname: Donaldson
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000403:Airway Resistance; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D020397:Goblet Cells / Q000473:pathology; D006965:Hyperplasia; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D007136:Immunoglobulins / Q000096:biosynthesis; D007249:Inflammation / Q000473:pathology; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008170:Lung Compliance; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000485:Allergens; D016207:Cytokines; C445241:IL-13 receptor alpha2-Fc fusion protein, Canis familiaris; D007141:Immunoglobulin Fc Fragments; D007136:Immunoglobulins; D018793:Interleukin-13; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin