Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity
| Autor: | Hans G. Folkesson, Richard M. Locksley, Martha L. Warnock, David J. Erle, David B. Corry, Jeanine P. Wiener-Kronish, Michael A. Matthay |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Ovalbumin
Messenger Immunology Priming (immunology) Enzyme-Linked Immunosorbent Assay Inbred C57BL SCID Immunoglobulin E Medical and Health Sciences Mice Interferon-gamma Antigen Cell Movement Respiratory Hypersensitivity Hydrostatic Pressure medicine 2.1 Biological and endogenous factors Animals Immunology and Allergy Lung Interleukin 5 Inbred BALB C Interleukin 4 biology Animal Inflammatory and immune system Interleukin respiratory system Eosinophil Asthma Acetylcholine respiratory tract diseases Eosinophils Immunoglobulin Isotypes medicine.anatomical_structure Disease Models Respiratory biology.protein RNA Interleukin-4 Interleukin-5 Antibody Pulmonary Ventilation Bronchoalveolar Lavage Fluid Biotechnology |
| Zdroj: | The Journal of experimental medicine, vol 183, iss 1 |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.183.1.109 |
| Popis: | Reversible airway hyperreactivity underlies the pathophysiology of asthma, yet the precise mediators of the response remain unclear. Human studies have correlated aberrant activation of T helper (Th) 2-like effector systems in the airways with disease. A murine model of airway hyperreactivity in response to acetylcholine was established using mice immunized with ovalbumin and challenged with aerosolized antigen. No airway hyperractivity occurred in severe combined immunodeficient mice. Identically immunized BALB/c mice developed an influx of cells, with a predominance of eosinophils and CD4+ T cells, into the lungs and bronchoalveolar lavage fluid at the time that substantial changes in airway pressure and resistance were quantitated. Challenged animals developed marked increases in Th2 cytokine production, eosinophil influx, and serum immunoglobulin E levels. Neutralization of interleukin (IL) 4 using monoclonal antibodies administered during the period of systemic immunization abrogated airway hyperractivity but had little effect on the influx of eosinophils. Administration of anti-IL-4 only during the period of the aerosol challenge did not affect the subsequent response to acetylcholine. Finally, administration of anti-IL-5 antibodies at levels that suppressed eosinophils to < 1% of recruited cells had no effect on the subsequent airway responses. BALB/c mice had significantly greater airway responses than C57BL/6 mice, consistent with enhanced IL-4 responses to antigen in BALB/c mice. Taken together, these data implicate IL-4 generated during the period of lymphocyte priming with antigen in establishing the cascade of responses required to generate airway hyperractivity to inhaled antigen. No role for IL-5 or eosinophils could be demonstrated. |
| Databáze: | OpenAIRE |
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