Inhibitory effects of anti-immunoglobulin E antibodies on airway remodeling in a murine model of chronic asthma.
BACKGROUND
Airway remodeling is one of the cardinal features of asthma and is thought to play a pivotal role in refractory or persistent asthma. Immunoglobulin E (IgE) has a major effect on the pathogenesis of asthma. The aim of this study was to investigate the effects of anti-IgE antibody not only on airway inflammation and bronchial hyperresponsiveness, but also on airway remodeling in a murine model of chronic asthma.


METHODS
The authors developed a mouse model of chronic asthma in which ovalbumin (OVA)-sensitized female BALB/c-mice were exposed to intranasal OVA administration twice a week for 3 months. Anti-IgE antibodies were administered intravenously starting on the 38th day and once a month thereafter for 3 months during the intranasal OVA challenge.


RESULTS
Mice that were chronically exposed to OVA developed sustained eosinophilic airway inflammation and airway hyperresponsiveness (AHR) to methacholine and showed increased levels of collagen, hydroxyproline, and alpha-smooth muscle actin, as compared with control mice. Treatment with anti-IgE antibody inhibited the development of AHR, eosinophilic inflammation, and airway remodeling. Moreover, anti-IgE antibody treatment reduced the levels of interleukin (IL)-5 and IL-13 in the bronchoalveolar lavage fluids, although it did not affect the levels of IL-10, transforming growth factor-beta, and activin A.


CONCLUSIONS
These results suggest that anti-IgE antibody treatment modulates the airway inflammation and remodeling associated with chronic allergen challenge. The inhibition of inflammation may be related to the regulation of Th2 cytokines. However, the mechanisms underlying the blocking of airway remodeling by anti-IgE antibody remain to be elucidated.
Kang
Ji Young
JY
Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, Korea.
Kim
Jin Woo
JW
Kim
Ju Sang
JS
Kim
Seung Joon
SJ
Lee
Sang Haak
SH
Kwon
Soon Suk
SS
Kim
Young Kyoon
YK
Moon
Hwa Sik
HS
Song
Jeong Sup
JS
Park
Sung Hak
SH
Lee
Sook Young
SY
D000199:Actins / Q000096:biosynthesis; D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002908:Chronic Disease; D003094:Collagen / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006909:Hydroxyproline / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin
D000199:Actins; D000888:Antibodies, Anti-Idiotypic; D016207:Cytokines; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D010047:Ovalbumin; D003094:Collagen; D006909:Hydroxyproline