Baglioni C, Phipps R J
Department of Biological Sciences, State University of New York, Albany 12222.
J Interferon Res. 1990 Oct;10(5):497-504. doi: 10.1089/jir.1990.10.497.
The effect of spraying the nasal mucosa with an aerosol of recombinant human interferon-alpha (IFN-alpha 2a) was studied in an animal model, the sheep, because cultures of sheep cells were found to be responsive to the antiviral activity of this IFN. Binding assays with 125I-labeled IFN-alpha 2a detected very few receptors in sheep nasal mucosa, but a membrane fraction prepared from this mucosa had abundant high-affinity receptors. Nasal mucosa homogenates were prepared from the turbinates of sheep that had been sprayed with IFN-alpha 2a aerosols, and the 2',5'-oligoadenylate (2-5A) activity induced in response was measured. To try to enhance the permeability of the mucosa, surfactant agents were added to the IFN and aerosols generated. There were measurable levels of 2-5A synthetase after aerosols with added sodium deoxycholate or, better, polyoxyethylene 9-lauryl ether. This latter surfactant was well tolerated in previous studies with intranasally administered insulin. The level of 2-5A synthetase induced was related to the dose of IFN, and the increased activity persisted up to 72 h after an IFN aerosol. These studies suggest that surfactant agents may make IFN aerosols much more effective for the prophylaxis of respiratory virus infections.
在动物模型绵羊中研究了用重组人α干扰素（IFN-α 2a）气雾剂喷洒鼻黏膜的效果，因为发现绵羊细胞培养物对这种干扰素的抗病毒活性有反应。用125I标记的IFN-α 2a进行的结合试验在绵羊鼻黏膜中检测到极少的受体，但从该黏膜制备的膜部分有丰富的高亲和力受体。从用IFN-α 2a气雾剂喷洒过的绵羊鼻甲制备鼻黏膜匀浆，并测量诱导产生的2',5'-寡腺苷酸（2-5A）活性。为了试图提高黏膜的通透性，将表面活性剂加入到干扰素和气雾剂中。在用脱氧胆酸钠或更好的聚氧乙烯9-月桂基醚添加气雾剂后有可测量水平的2-5A合成酶。后一种表面活性剂在先前经鼻给予胰岛素的研究中耐受性良好。诱导产生的2-5A合成酶水平与干扰素剂量有关，并且在干扰素气雾剂后活性增加持续长达72小时。这些研究表明表面活性剂可能使干扰素气雾剂对预防呼吸道病毒感染更有效。
