Role of Th2 responses in the development of allergen-induced airway remodelling in a murine model of allergic asthma.
(1) To clarify the involvement of Th2 responses in the development of allergen-induced airway remodelling, we investigated the effect of anti-CD4 monoclonal antibody (mAb) and anti-CD8 mAb, and the responses of IL-4 gene-knockout (KO) mice in a murine model of allergic asthma. (2) Mice were immunized twice by intraperitoneal injections of ovalbumin (OA), and exposed to aeroallergen (OA, 1% w v(-1)) for 3 weeks. Twenty-four hours after the final challenge, airway responsiveness to acetylcholine was measured, and bronchoalveolar lavage (BAL) and histological examinations were carried out. (3) Anti-CD4 mAb (1 mg kg(-1)) clearly inhibited allergen-induced increases in airway responsiveness to acetylcholine, the number of eosinophils in BAL fluid, serum OA-specific IgE levels, IL-13 and transforming growth factor-beta1 levels in BAL fluid, and amount of hydroxyproline in the lung by 100, 99, 100, 100, 84, and 60%, respectively. Furthermore, the antibody (1 mg kg(-1)) also attenuated allergen-induced goblet cell hyperplasia in the epithelium and subepithelial fibrosis by 72 and 83%, respectively. In contrast, anti-CD8 mAb (1 mg kg(-1)) showed no effect on each parameter. Furthermore, all these parameters were attenuated in IL-4KO mice by 57, 93, 100, 45, 84 and 60%, and also 72 and 83%, respectively. (4) These findings suggest that Th2 responses play a critical role for the development of allergen-induced airway remodelling, and that the inhibition of Th2 responses, e.g. using anti-CD4 mAb, is a therapeutic approach for the treatment of airway remodelling in asthma.
Komai
Masato
M
Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
Tanaka
Hiroyuki
H
Masuda
Taisei
T
Nagao
Koichi
K
Ishizaki
Masayuki
M
Sawada
Masatsugu
M
Nagai
Hiroichi
H
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens; D005260:Female; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology*; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D015704:CD4 Antigens; D016827:CD8 Antigens; D015847:Interleukin-4; D010047:Ovalbumin