Interleukin-4 receptor blockade prevents airway responses induced by antigen challenge in mice

作者：Stephen H. Gavett, Daniel J. O’Hearn, Christopher L. Karp, Ethan Patel, Brian Schofield, Fred D. Finkelman, Marsha A. Wills-Karp · 发表于：American Journal of Physiology-Lung Cellular and Molecular Physiology · 年份：1997 · DOI：10.1152/ajplung.1997.272.2.l253 · 被引用次数：201 · 研究领域：Asthma and respiratory diseases、Respiratory and Cough-Related Research、Pediatric health and respiratory diseases

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.