Gavett S H, O'Hearn D J, Karp C L, Patel E A, Schofield B H, Finkelman F D, Wills-Karp M
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
Am J Physiol. 1997 Feb;272(2 Pt 1):L253-61. doi: 10.1152/ajplung.1997.272.2.L253.
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.
研究了白细胞介素（IL）-4在小鼠对绵羊红细胞（SRBC）致敏和激发后气道高反应性（AHR）及肺部嗜酸性粒细胞增多症发展过程中的功能作用。在气管内给予抗原或仅给予赋形剂进行激发前3天，用抗小鼠IL-4受体抗体（抗IL-4R）处理对照和SRBC致敏的A/J小鼠。阻断IL-4R可显著降低抗原诱导的AHR，并防止杯状细胞和支气管肺泡灌洗（BAL）嗜酸性粒细胞增多。用抗IL-4R处理并不影响抗原诱导的肺中IL-5、干扰素-γ或IL-4 mRNA以及BAL蛋白水平的升高，但确实显著提高了IL-4蛋白水平。用抗黏附分子抗体（血管细胞黏附分子-1和极迟活化抗原-4）处理不能降低抗原诱导的AHR。在7天时间内给予IL-4不会增加未致敏小鼠的气道反应性，也不会引起BAL细胞数量的任何变化。这些结果表明，IL-4是抗原诱导的AHR、杯状细胞化生和肺部嗜酸性粒细胞增多症体内发展所必需的。
