Critical role for IL-13 in the development of allergen-induced airway hyperreactivity

Airway hyperresponsiveness to a variety of specific and nonspecific stimuli is a cardinal feature of asthma, which affects nearly 10% of the populatio n in industrialized countries. Eosinophilic pulmonary inflammation, eosinop hil-derived products, as well as Th2 cytokines IL-13, IL-4, and IL-5, have been associated with the development of airway hyperreactivity (AHR), but t he specific immunological basis underlying the development of AHR remains c ontroversial. Herein we show that mice with targeted deletion of IL-13 fail ed to develop allergen-induced AHR, despite the presence of vigorous Th2-bi ased, eosinophilic pulmonary inflammation. However, AHR was restored in IL- 13(-/-) mice by the administration of recombinant IL-13. Moreover, adoptive transfer of OVA-specific Th2 cells generated from TCR-transgenic IL-13(-/- ) mice failed to induce AHR in recipient SCID mice, although such IL-13(-/- ) Th2 cells produced high levels of IL-4 and IL-5 and induced significant a irway inflammation. These studies definitively demonstrate that IL-13 is ne cessary and sufficient for the induction of AHR and that eosinophilic airwa y inflammation in the absence of IL-13 is inadequate for the induction of A HR. Therefore, treatment of human asthma with antagonists of IL-13 may be v ery effective.