title: Anti-interleukin-9 antibody treatment inhibits airway inflammation and hyperreactivity in mouse asthma model.
abstract: Numerous in vitro and in vivo studies in both animals and patients with asthma have shown that interleukin (IL)-9 is an important inflammatory mediator in asthma. To examine the effects of IL-9 antagonism on airway inflammation, ovalbumin-sensitized BALB/c mice were intravenously given anti-IL-9 antibody or an isotype-matched control antibody 30 minutes before challenge with aerosolized ovalbumin. Airway response to methacholine was measured, and samples of bronchoalveolar lavage fluid (BALF) were obtained 24 hours after the last antigen challenge. Lung tissue was harvested and examined histopathologically. After ovalbumin challenge, there were significant increases in airway hyperreactivity, the numbers of inflammatory cells in lung, and IL-4, IL-5, and IL-13 production in BALF. Treatment with anti-IL-9 antibody significantly prevented airway hyperreactivity in response to methacholine inhalation. Blockade of IL-9 reduced the numbers of eosinophils (0.3 +/- 0.1 x 10(5) and 23.6 +/- 0.5 x 10(5)/ml, anti-IL-9 antibody/control immunoglobulin G) and lymphocytes (0.2 +/- 0.2 x 10(5) and 0.8 +/- 0.1 x 10(5)/ml) in BALF. Anti-IL-9 antibody treatment also reduced the concentrations of IL-4 (from 70.6 +/- 4.6 to 30.8 +/- 5.2 pg/ml), IL-5 (from 106.4 +/- 12 to 54.4 +/- 6.6 pg/ml), and IL-13 (from 44.2 +/- 7.6 to 30.1 +/- 5.5 pg/ml) in BALF. Macrophage-derived cytokine expression in the airways was also decreased by IL-9 blockade. Taken together, our findings emphasize the importance of IL-9 in the pathogenesis of asthma and suggest that blockade of IL-9 may be a new therapeutic strategy for bronchial asthma.
authors.affiliation: Department of Pulmonary Medicine, Dokkyo University School of Medicine, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan. cheng@dokkyomed.ac.jp
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.forename: Masafumi
authors.initials: M
authors.lastname: Arima
authors.forename: Kyoko
authors.initials: K
authors.lastname: Honda
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Hirata
authors.forename: Fukiko
authors.initials: F
authors.lastname: Eda
authors.forename: Nozomi
authors.initials: N
authors.lastname: Yoshida
authors.forename: Fumiya
authors.initials: F
authors.lastname: Fukushima
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016906:Interleukin-9 / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012137:Respiratory System / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000906:Antibodies; D016906:Interleukin-9