Takano H, Lim H B, Miyabara Y, Ichinose T, Yoshikawa T, Sagai M
Research Team for Health Effects of Air Pollutants, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
J Pharmacol Exp Ther. 1998 Aug;286(2):767-71.
The role of nitric oxide in the airway hyperresponsiveness and inflammation of bronchial asthma has not yet been established. However, L-arginine, the substrate for nitric oxide synthases, reportedly alleviates airway hyperresponsiveness caused by parainfluenza virus and reduces granulocytic inflammation induced by ischemia-reperfusion. We investigated the effects of L-arginine on a murine model of allergic asthma that included airway hyperresponsiveness, eosinophilic inflammation and expression of interleukin (IL)-5 in the lung. The mice received drinking water with or without L-arginine for 9 weeks. Histologic evaluation and cellular profiles in bronchoalveolar lavage fluid showed that p.o. administration of L-arginine (72 micromol/kg/day) significantly enhanced eosinophilic airway inflammation and goblet cell proliferation that were associated with intratracheal instillation of ovalbumin. L-Arginine also increased protein levels of IL-5 and IL-2 in supernatants from the lung exposed to ovalbumin. The number of eosinophils in bronchoalveolar lavage fluid correlated significantly with the expression of IL-5. L-Arginine did not reverse ovalbumin-associated airway hyperresponsiveness to inhaled ACh. These results suggest that p.o. administration of L-arginine aggravates allergen-induced eosinophilic airway inflammation via expression of IL-5, and in this model it does not show therapeutic efficacy against airway hyperresponsiveness associated with allergen exposure. Oral administration of L-arginine, the precursor of nitric oxide, may not be an effective intervention in allergic asthma.
一氧化氮在支气管哮喘气道高反应性和炎症中的作用尚未明确。然而，据报道，一氧化氮合酶的底物L-精氨酸可减轻副流感病毒引起的气道高反应性，并减轻缺血再灌注诱导的粒细胞炎症。我们研究了L-精氨酸对过敏性哮喘小鼠模型的影响，该模型包括气道高反应性、嗜酸性粒细胞炎症以及肺中白细胞介素（IL）-5的表达。小鼠饮用含或不含L-精氨酸的水9周。组织学评估和支气管肺泡灌洗液中的细胞分布显示，口服L-精氨酸（72微摩尔/千克/天）显著增强了与气管内注入卵清蛋白相关的嗜酸性气道炎症和杯状细胞增殖。L-精氨酸还增加了暴露于卵清蛋白的肺上清液中IL-5和IL-2的蛋白水平。支气管肺泡灌洗液中嗜酸性粒细胞的数量与IL-5的表达显著相关。L-精氨酸并未逆转卵清蛋白相关的气道对吸入乙酰胆碱的高反应性。这些结果表明，口服L-精氨酸通过IL-5的表达加重了变应原诱导的嗜酸性气道炎症，并且在该模型中，它对与变应原暴露相关的气道高反应性未显示出治疗效果。口服一氧化氮的前体L-精氨酸可能不是过敏性哮喘的有效干预措施。
