Interleukin (IL)-5 but not immunoglobulin E reconstitutes airway inflammation and airway hyperresponsiveness in IL-4-deficient mice.
We studied the role of interleukin (IL)-4, IL-5, and allergen-specific immunoglobulin (Ig) E in the development of allergen-induced sensitization, airway inflammation, and airway hy-perresponsiveness (AHR). Normal, IL-4-, and IL-5-deficient C57BL/6 mice were sensitized intraperitoneally to ovalbumin (OVA) and repeatedly challenged with OVA via the airways. After allergen sensitization and airway challenge, normal and IL-5-deficient, but not IL-4-deficient, mice developed increased serum levels of total and antigen-specific IgE levels and increased IL-4 production in the lung tissue compared with nonsensitized control mice. Only normal mice showed significantly increased IL-5 production in the lung tissue and an eosinophilic infiltration of the peribronchial regions of the airways, whereas both IL-4- and IL-5-deficient mice had little or no IL-5 production and no significant eosinophilic airway inflammation. Associated with the inflammatory responses in the lung, only normal mice developed increased airway responsiveness to methacholine after sensitization and airway challenge; in both IL-4- and IL-5-deficient mice, airway responsiveness was similar to that in nonsensitized control mice. Reconstitution of sensitized, IL-4-deficient mice before allergen airway challenge with IL-5, but not with allergen-specific IgE, restored eosinophilic airway inflammation and the development of AHR. These data demonstrate the importance of IL-4 for allergen-driven airway sensitization and that IL-5, but not allergen-specific IgE, is required for development of eosinophilic airway inflammation and AHR after this mode of sensitization and challenge.
Hamelmann
E
E
Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA.
Takeda
K
K
Haczku
A
A
Cieslewicz
G
G
Shultz
L
L
Hamid
Q
Q
Xing
Z
Z
Gauldie
J
J
Gelfand
E W
EW
D000818:Animals; D000906:Antibodies / Q000097:blood; D004804:Eosinophils / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology*; D015848:Interleukin-5 / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology*
D000906:Antibodies; D007074:Immunoglobulin G; D015848:Interleukin-5; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin