Soluble IL-4 receptor inhibits airway inflammation following allergen challenge in a mouse model of asthma
Soluble IL-4 receptor inhibits airway inflammation following allergen challenge in a mouse model of asthma
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DOI：
10.4049/jimmunol.164.2.1086
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发表时间：
2000-01-15
影响因子：
4.4
通讯作者：
Maliszewski, CR
中科院分区：
文献类型：
--
作者：
Henderson, WR;Chi, EY;Maliszewski, CR
在体外和体内研究中，在动物模型和人哮喘中，IL-4是哮喘中的重要炎症介质。在小鼠哮喘模型中，我们检测了可溶性IL-4 R（sIL-4 R）的抗炎活性。在该模型中，通过i. p.和鼻内（i.n.）通过i.n.局OVA激发激发嗜酸性粒细胞浸润到肺中，伴随气道的广泛粘液阻塞，并导致支气管高反应性。sIL-4 R（0.1-100 μ g）通过i.n.或腹腔注射途径。与对照组相比，经i.n.给药后，血和支气管肺泡灌洗液中sIL-4 R水平均显著升高。腹膜内注射100 μ g sIL-4 R仅提高血液中sIL-4 R的水平。I. N.在过敏原攻击前给予100 μ g sIL-4 R显著减少晚期肺部炎症，阻断气道嗜酸性粒细胞浸润、VCAM-1表达和粘液分泌过多。相反，100 μ g sIL-4 R的腹膜内递送仅抑制嗜酸性粒细胞流入肺，但不抑制气道粘液释放。此外，通过i. n.或i. p.途径不能降低对乙酰甲胆碱激发的气道高反应性。因此，通过给予外源性sIL-4 R提高气道sIL-4 R水平可有效阻断在该小鼠变应原激发哮喘模型中发生的晚期肺部炎症。这些结果表明，sIL-4 R在哮喘患者中可能具有有益的抗炎作用。
In vitro and in vivo studies, in both animal models and human asthmatics, have implicated IL-4 as an important inflammatory mediator in asthma, In a murine asthma model, we examined the anti-inflammatory activities of soluble IL-4R (sIL-4R). In this model, mice sensitized to OVA by i.p. and intranasal (i.n.) routes are challenged with the allergen by i.n. administration. The OVA challenge elicits an eosinophil infiltration into the lungs, with widespread mucus occlusion of the airways, and results in bronchial hyperreactivity. sIL-4R (0.1-100 mu g) was administered by either i.n. or i.p. routes before OVA challenge in OVA-sensitized mice. Both blood and bronchoalveolar lavage fluid levels of sIL-4R were significantly elevated compared with controls by i.n. delivery of 100 mu g sIL-4R; i.p. delivery of 100 mu g sIL-4R only raised blood levels of sIL-4R. The i.n. administration of 100 mu g sIL-4R before allergen challenge significantly reduced late phase pulmonary inflammation, blocking airway eosinophil infiltration, VCAM-1 expression, and mucus hypersecretion. in contrast, i.p. delivery of 100 mu g sIL-4R inhibited only the influx of eosinophils into the lungs, but not airway mucus release. Furthermore, sIL-4R treatment by either i.n. or i.p. routes did not reduce airway hyperreactivity in response to methacholine challenge. Thus, elevating airway levels of sIL-4R through the administration of exogenous sIL-4R is effective in blocking the late phase pulmonary inflammation that occurs in this murine allergen-challenge asthma model. These results suggest that sIL-4R may have beneficial anti-inflammatory effects in asthmatic patients.