Effect of anti-mIL-9 antibody on the development of pulmonary inflammation and airway hyperresponsiveness in allergic mice.
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.
Kung
T T
TT
Department of Allergy, Schering-Plough Research Institute, Kenilworth, New Jersey 07003, USA. ted.kung@spcorp.com
Luo
B
B
Crawley
Y
Y
Garlisi
C G
CG
Devito
K
K
Minnicozzi
M
M
Egan
R W
RW
Kreutner
W
W
Chapman
R W
RW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D020397:Goblet Cells / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics; D018793:Interleukin-13 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D016906:Interleukin-9 / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000276:immunology
D000911:Antibodies, Monoclonal; D018793:Interleukin-13; D015848:Interleukin-5; D016906:Interleukin-9; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin