Complete inhibition of allergic airway inflammation and remodelling in quadruple IL-4/5/9/13-/- mice.
BACKGROUND
T-helper type 2 (Th2)-derived cytokines such as IL-4, IL-5, IL-9 and IL-13 play an important role in the synthesis of IgE and in the promotion of allergic eosinophilic inflammation and airway wall remodelling.


OBJECTIVE
We determined the importance of IL-13 alone, and of the four Th2 cytokines together, by studying mice in which either IL-13 alone or the Th2 cytokine cluster was genetically disrupted.


METHODS
The knock-out mice and their BALB/c wild-type (wt) counterparts were sensitized and repeatedly exposed to ovalbumin (OVA) aerosol.


RESULTS
Bronchial responsiveness measured as the concentration of acetylcholine aerosol needed to increase baseline lung resistance by 100% (PC100) was decreased in IL-13-/-, but increased in IL-4/5/9/13-/- mice. Chronic allergen exposure resulted in airway hyperresponsiveness (AHR) in wt mice but not in both genetically modified mice. After allergen exposure, eosinophil counts in bronchoalveolar lavage fluid and in airways mucosa, and goblet cell numbers were not increased in IL-4/5/9/13-/- mice, and were only attenuated in IL-13-/- mice. Airway smooth muscle (ASM) hyperplasia after allergen exposure was prevented in both IL-13-/- and IL-4/5/9/13-/- mice to an equal extent. Similarly, the rise in total or OVA-specific serum IgE levels was totally inhibited.


CONCLUSIONS
IL-13 is mainly responsible for AHR, ASM hyperplasia and increases in IgE, while IL-4, -5 and -9 may contribute to goblet cell hyperplasia and eosinophilic inflammation induced by chronic allergen exposure in a murine model. Both redundancy or complementariness of Th2 cytokines can occur in vivo, according to specific aspects of the allergic response.
Nath
Puneeta
P
Experimental Studies, Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
Leung
Sum Yee
SY
Williams
Alison S
AS
Noble
Alistair
A
Xie
Shaoping
S
McKenzie
Andrew N J
AN
Chung
Kian Fan
KF
D000109:Acetylcholine / Q000008:administration & dosage; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001991:Bronchitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020397:Goblet Cells / Q000276:immunology; D006965:Hyperplasia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D018793:Interleukin-13 / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology; D015848:Interleukin-5 / Q000235:genetics / Q000502:physiology; D016906:Interleukin-9 / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000276:immunology / Q000473:pathology; D011657:Pulmonary Eosinophilia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000276:immunology / Q000473:pathology
D000485:Allergens; D018793:Interleukin-13; D015848:Interleukin-5; D016906:Interleukin-9; D015847:Interleukin-4; D007073:Immunoglobulin E; D000109:Acetylcholine