Effect of Anti-mIL-9 Antibody on the Development of Pulmonary Inflammation and Airway Hyperresponsiveness in Allergic Mice

• Published in: American journal of respiratory cell and molecular biology Vol. 25; no. 5; pp. 600 - 605
• Main Authors: Kung, Ted T, Luo, Bin, Crawley, Yvette, Garlisi, Charles G, Devito, Kristine, Minnicozzi, Michael, Egan, Robert W, Kreutner, William, Chapman, Richard W
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01.11.2001
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Bronchial Hyperreactivity - immunology; Bronchoalveolar Lavage Fluid - immunology; Eosinophils - immunology; Gene Expression - immunology; Goblet Cells - immunology; Hypersensitivity - immunology; Immunoglobulin E - blood; Interferon-gamma - genetics; Interleukin-13 - genetics; Interleukin-4 - genetics; Interleukin-5 - genetics; Interleukin-9 - immunology; Male; Mice; Mice, Inbred Strains; Ovalbumin - immunology; Ovalbumin - pharmacology; Pneumonia - immunology; Respiratory Mucosa - immunology; RNA, Messenger - analysis
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/ajrcmb.25.5.4533

Interleukin (IL)-9 is a T-cell-derived cytokine with pleiotropic activities on T helper 2 cells, B cells, and mast cells. IL-9 may therefore play an important role in the development of allergic pulmonary inflammatory diseases. In this study, an antimouse IL-9 (anti-mIL-9) antibody (Ab) was evaluated against pulmonary eosinophilia, histopathologic changes in lung tissues, serum immunoglobulin (Ig) E levels, and airway hyperresponsiveness (AHR) to methacholine in mice sensitized and challenged with ovalbumin (OVA). Additionally, steady-state levels of IL-4, IL-5, IL-13, and interferon-gamma messenger RNA (mRNA) in the lungs were measured. The anti-mIL-9 Ab (200 microg/mouse, intraperitoneally) was given as either four doses during the sensitization period or as a single dose before OVA challenge. Sensitized mice challenged with OVA displayed marked pulmonary eosinophilia, epithelial damage, and goblet cell hyperplasia. OVA challenge also increased mRNA levels of IL-4, IL-5, and IL-13 in the lungs. AHR was also increased twofold in sensitized, challenged mice. Treatment of sensitized, challenged mice with four doses of anti-mIL-9 Ab significantly reduced pulmonary eosinophilia, serum IgE levels, goblet cell hyperplasia, airway epithelial damage, and AHR, but had no effect on IL-4, IL-5, and IL-13 mRNA levels in the lungs. A single dose of the antibody was ineffective on all measures. These results indicate that an antibody to mIL-9 inhibits the development of allergic pulmonary inflammation and AHR in mice.