THE ROLE OF INTERLEUKIN-13 IN ESTABLISHED ALLERGIC AIRWAY DISEASE

Abstract

Taube C, Duez C, Cui Z, et al. J Immunol. 2002;169:6482–6489To determine the effects of blocking interleukin-13 (IL-13) on early- and late-phase airway responses in previously sensitized and challenged mice.Ovalbumin-sensitized and -challenged mice were studied.Ten- to 12-week-old mice were sensitized with intraperitoneal injections of ovalbumin on days 1 and 14 and then challenged with nebulized ovalbumin for 3 days on days 28 to 30. The mice received a second challenge of nebulized ovalbumin 6 weeks after the first challenge, to assess inflammatory and histologic outcomes, airway reactivity, and early- and late-phase responses. A soluble fusion protein consisting of the extracellular domain of the high-affinity IL-13 receptor (IL-13R) and human immunoglobulin G (hIgG) (sIL-13Rα2-hIgG) was administered 24 hours and 1 hour before the second ovalbumin challenge, when early- and late-phase responses, respectively, were assessed, and was also administered 24 hours after the challenge, when inflammatory and histologic outcomes and airway reactivity at 48 hours were assessed. hIgG was administered to control mice.Levels of IL-13 in bronchoalveolar lavage (BAL) fluid were increased after the second ovalbumin challenge in previously sensitized mice, and sIL-13Rα2-hIgG significantly reduced BAL fluid levels of IL-13. The sIL-13Rα2-hIgG fusion protein also inhibited the development of the late-phase response but not the early-phase response. Airway hyperresponsiveness, assessed as changes in lung resistance and dynamic compliance after methacholine inhalation, was inhibited by sIL-13Rα2-hIgG fusion protein. sIL-13Rα2-hIgG decreased the number of cells in BAL fluid, particularly eosinophils, but did not completely eliminate them. Treatment with sIL-13Rα2-hIgG significantly reduced BAL fluid levels of IL-5 but not interferon-γ, IL-12, or IL-10.IL-13 appears to play a critical role in the development of the late-phase response in previously sensitized mice. Blockade of IL-13 may be an important strategy to pursue in the development of new treatments for allergic asthma.Although this study was performed in mice, the results provide the foundation for pursuing IL-13 as a target for asthma treatment. The hope is that targeted therapy may be associated with fewer side effects than corticosteroid therapy and that treatment may be able to be tailored to specific asthma phenotypes.