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Am. J. Respir. Cell Mol. Biol., Volume 25, Number 5, November, 2001 600-605

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

Ted T. Kung, Bin Luo, Yvette Crawley, Charles G. Garlisi, Kristine Devito, Michael Minnicozzi, Robert W. Egan, William Kreutner, and Richard W. Chapman

Department of Allergy, Schering-Plough Research Institute, Kenilworth, New Jersey

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 µg/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.

Abbreviations: airway hyperresponsiveness, AHR; anti-mouse IL-9 monoclonal antibody, anti-mIL-9 mAb; bronchoalveolar lavage, BAL; BAL fluid, BALF; complementary DNA, cDNA; eosinophil, EO; immunoglobulin, Ig; interferon gamma, IFN-gamma ; interleukin, IL; messenger RNA, mRNA; methacholine, MCh; ovalbumin, OVA; periodic acid-Schiff/alcan blue, PAS/AB; provocative dose of methacholine increasing respiratory resistance by 100% above baseline, PD100; polymerase chain reaction, PCR; airway resistance, Raw; standard error of the mean, SEM; T helper, Th.




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