[Functional molecules in allergic bronchial asthma].
Bronchial asthma is considered to be a chronic airway inflammatory disease, characterized by airway obstruction, airway eosinophilic inflammation, and airway hyperresponsiveness (AHR) to a variety of stimuli. AHR is thought to be an important symptom, because the severity of the disease is generally correlated with the degree of AHR. Recent clinical studies have demonstrated the involvement of airway inflammation in the development of allergen-induced AHR, although, the mechanism of allergen-induced AHR has not been fully elucidated and remains controversial. In vivo animal models might provide important information on this point. We have established a mouse model of allergic asthma, which is characterized by airway eosinophilia, IgE production, T helper type 2 (Th2) cytokine production in the airway, and AHR, and investigated the role of inflammatory cells and functional molecules. Results from gene-knockout and mutant mice demonstrated the involvement of T cells, mast cells, prostanoids, and Th2 cytokines including interleukin (IL)-4 and IL-5 in the development of allergen-induced airway inflammation and AHR. In contrast, treatment with anti-IL-4 monoclonal antibody (mAb) or anti-IL-5 mAb during allergen inhalation did not inhibit allergen-induced AHR, although the combination of these mAbs clearly inhibited the enhanced responsiveness. These data indicate that it is a better strategy for control of the disease to inhibit or suppress multifunctional molecules like corticosteroids rather than to inhibit a single factor, because bronchial asthma is a multifactorial disease.
Tanaka
Hiroyuki
H
Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502-8585, Japan. hirotnk@gifu-ppu.ac.jp
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells
D000485:Allergens; D015848:Interleukin-5; D015847:Interleukin-4