The Role of IL-13 in Established Allergic Airway Disease

• DOI: 10.4049/jimmunol.169.11.6482
• Publication Date: 2014-04-20T23:41:24Z
• Authors: Christian Taube; Catherine Duez; Zhi-Hua Cui; Katsuyuki Takeda; Yeong-Ho Rha; Jung-Won Park; Annette Balhorn; Debra D. Donaldson; Azzeddine Dakhama; Erwin W. Gelfand
• Keywords: Inflammation; 0301 basic medicine; Mice, Inbred BALB C; Hyperplasia; Interleukin-13; Time Factors; Ovalbumin; Airway Resistance; Recombinant Fusion Proteins; 610; Immunoglobulins; Receptors, Interleukin; Allergens; Immunoglobulin Fc Fragments; Mice; 03 medical and health sciences; Respiratory Hypersensitivity; Animals; Cytokines; Female; Goblet Cells; Bronchoalveolar Lavage Fluid; Lung Compliance

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-13Rα2-IgG fusion protein (sIL-13Rα2Fc) on days 71–72 for the early and late responses and on days 71–73 for the development of AHR. sIL-13Rα2Fc administration inhibited the late, but not early, phase response and the OVA challenge-induced changes in lung resistance and dynamic compliance; as well, sIL-13Rα2Fc 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.