Musoh K, Maeda Y, Tanaka H, Inagaki N, Nagai H
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Pharmacology. 2000 Aug;61(2):70-7. doi: 10.1159/000028383.
The effects of a newly synthesized anti-allergic agent, HSR-609, on allergic airway hyperresponsiveness and airway inflammation have been studied in sensitized mice. The effects were compared with those of two histamine H(1) receptor antagonists, cetirizine and terfenadine, and prednisolone. Three inhalations of antigen caused an increase in leukocytes (including eosinophils) with increases in IL-5 in BALF and airway hyperresponsiveness to acetylcholine in BALB/c mice. All drugs were orally administered once a day for 10 days from the day before the first inhalation of antigen. HSR-609 (10 mg/kg) and prednisolone (5 mg/kg) significantly inhibited the antigen-induced airway hyperresponsiveness, whereas cetirizine (10 mg/kg) or terfenadine (100 mg/kg) did not affect this airway response. At the same time HSR-609 inhibited the antigen-induced eosinophilia and IL-5 production in BALF. Prednisolone also showed an inhibitory effect on the airway eosinophilia and IL-5 production but not cetirizine and terfenadine in the same experiments. In addition, HSR-609 (p.o.) dose-dependently suppressed the accumulation of eosinophils elicited by antigen-stimulated D10G4.1 cells, a murine Th2 clone, in peritoneal cavity lavage fluid in AKR/J mice. These results suggest that HSR-609 inhibits allergic airway hyperresponsiveness to acetylcholine probably because of the inhibition of Th2-dependent eosinophilia caused by IL-5. In addition, effects of HSR-609 were different from those of cetirizine and terfenadine concerning the inhibition of antigen-induced airway hyperresponsiveness in mice.
在致敏小鼠中研究了一种新合成的抗过敏药物HSR-609对过敏性气道高反应性和气道炎症的影响。将其效果与两种组胺H(1)受体拮抗剂西替利嗪和特非那定以及泼尼松龙进行了比较。对BALB/c小鼠进行三次抗原吸入后，其白细胞（包括嗜酸性粒细胞）数量增加，BALF中的IL-5增加，对乙酰胆碱的气道高反应性增强。从第一次吸入抗原的前一天开始，所有药物均每天口服一次，持续10天。HSR-609（10mg/kg）和泼尼松龙（5mg/kg）显著抑制抗原诱导的气道高反应性，而西替利嗪（10mg/kg）或特非那定（100mg/kg）对这种气道反应没有影响。同时，HSR-609抑制抗原诱导的BALF中嗜酸性粒细胞增多和IL-5产生。在相同实验中，泼尼松龙也对气道嗜酸性粒细胞增多和IL-5产生有抑制作用，但西替利嗪和特非那定则没有。此外，HSR-609（口服）剂量依赖性地抑制了抗原刺激的小鼠Th2克隆D10G4.1细胞在AKR/J小鼠腹腔灌洗液中引起的嗜酸性粒细胞积聚。这些结果表明，HSR-609可能通过抑制IL-5引起的Th2依赖性嗜酸性粒细胞增多来抑制对乙酰胆碱的过敏性气道高反应性。此外，在抑制小鼠抗原诱导的气道高反应性方面，HSR-609的作用与西替利嗪和特非那定不同。
