Abstract
The functional role of interleukin (IL)-4 in the development of airway hyperresponsiveness (AHR) and pulmonary eosinophilia in response to sensitization and challenge of mice with sheep red blood cells (SRBC) was examined. Control- and SRBC-sensitized A/J mice were treated with an antibody to the murine IL-4 receptor (anti-IL-4R) 3 days before intratracheal challenge with the antigen or vehicle only. Blockade of IL-4R significantly reduced antigen-induced AHR and prevented increases in goblet cells and bronchoalveolar lavage (BAL) eosinophils. Treatment with anti-IL-4R did not affect antigen-induced increases in lung mRNA and BAL protein levels of IL-5 and interferon-gamma or IL-4 mRNA but did significantly increase IL-4 protein levels. Antigen-induced AHR was not reduced by treatment with antibodies to the adhesion molecules, vascular cell adhesion molecule-1 and very late activation antigen-4. Administration of IL-4 over a 7-day period did not increase airway reactivity or induce any changes in BAL cell numbers in naive mice. These results demonstrate that IL-4 is necessary for in vivo development of antigen-induced AHR, goblet cell metaplasia, and pulmonary eosinophilia.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-Allergic Agents / immunology
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Antibodies, Monoclonal / immunology
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Antigen-Antibody Complex / immunology
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Antigens / immunology*
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Antigens, CD / drug effects*
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Antigens, CD / immunology
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Bronchoalveolar Lavage Fluid / chemistry
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Cytokines / genetics
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Cytokines / metabolism
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Integrin alpha4beta1
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Integrins / immunology
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Interleukin-4 / immunology
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Lung / pathology
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Male
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Mice
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Mice, Inbred Strains
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RNA, Messenger / metabolism
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Receptors, Interleukin / antagonists & inhibitors*
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Receptors, Interleukin / drug effects*
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Receptors, Interleukin / immunology
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Receptors, Interleukin-4
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Receptors, Lymphocyte Homing / immunology
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Recombinant Proteins
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Respiratory Hypersensitivity / immunology*
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Respiratory Hypersensitivity / pathology
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Respiratory Hypersensitivity / prevention & control*
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Vascular Cell Adhesion Molecule-1 / immunology
Substances
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Anti-Allergic Agents
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Antibodies, Monoclonal
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Antigen-Antibody Complex
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Antigens
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Antigens, CD
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Cytokines
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Integrin alpha4beta1
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Integrins
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RNA, Messenger
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Receptors, Interleukin
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Receptors, Interleukin-4
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Receptors, Lymphocyte Homing
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Recombinant Proteins
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Vascular Cell Adhesion Molecule-1
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Interleukin-4