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 population in industrialized countries. Eosinophilic pulmonary inflammation, eosinophil-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 the specific immunological basis underlying the development of AHR remains controversial. Herein we show that mice with targeted deletion of IL-13 failed to develop allergen-induced AHR, despite the presence of vigorous Th2-biased, 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 airway inflammation. These studies definitively demonstrate that IL-13 is necessary and sufficient for the induction of AHR and that eosinophilic airway inflammation in the absence of IL-13 is inadequate for the induction of AHR. Therefore, treatment of human asthma with antagonists of IL-13 may be very effective.
Walter
D M
DM
Division of Immunology and Allergy, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
McIntire
J J
JJ
Berry
G
G
McKenzie
A N
AN
Donaldson
D D
DD
DeKruyff
R H
RH
Umetsu
D T
DT
D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000818:Animals; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D018793:Interleukin-13 / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D018418:Th2 Cells / Q000637:transplantation
D000485:Allergens; D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin