Soluble IL-4 receptor inhibits airway inflammation following allergen challenge in a mouse model of asthma

In vitro and in vivo studies, in both animal models and human asthmatics, h ave implicated IL-4 as an important inflammatory mediator in asthma, In a m urine 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 intranas al (i.n.) routes are challenged with the allergen by i.n. administration. T he OVA challenge elicits an eosinophil infiltration into the lungs, with wi despread mucus occlusion of the airways, and results in bronchial hyperreac tivity. sIL-4R (0.1-100 mu g) was administered by either i.n. or i.p. route s before OVA challenge in OVA-sensitized mice. Both blood and bronchoalveol ar 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 pulmonar y inflammation, blocking airway eosinophil infiltration, VCAM-1 expression, and mucus hypersecretion. in contrast, i.p. delivery of 100 mu g sIL-4R in hibited 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 n ot reduce airway hyperreactivity in response to methacholine challenge. Thu s, elevating airway levels of sIL-4R through the administration of exogenou s sIL-4R is effective in blocking the late phase pulmonary inflammation tha t occurs in this murine allergen-challenge asthma model. These results sugg est that sIL-4R may have beneficial anti-inflammatory effects in asthmatic patients.