{"title":"半胱氨酸白三烯不介导豚鼠脂多糖诱导的气道高反应性","authors":"Takashi Uno, Hiroyuki Tanaka, Hiroichi Nagai","doi":"10.1016/S0090-6980(96)00126-8","DOIUrl":null,"url":null,"abstract":"<div><p>Inhalation of bacterial lipopolysaccharide (LPS) by guinea pigs caused bronchial hyperreactivity to acetylcholine with a peak at 2 hr after exposure. Exposure to 0.01% LPS for 30 min resulted in an elevation of cysteinyl leukotrienes (cys-LTs) content in bronchoalveolar lavage fluid (BALF) which was obtained 1 hr after LPS exposure. The cys-LTs antagonist, ONO-1078 (10 mg/kg, p.o.), significantly inhibited LPS-induced bronchial hyperreactivity, but ICI-204,219 (10 mg/kg, p.o.), another cys-LT antagonist, did not. Each dose employed in the present study was sufficient to inhibit LTD<sub>4</sub> induced broncho-constriction in guinea pigs. In order to investigate the inhibitory mechanism of ONO-1078, the effect on the LPS-induced production of tumor necrosis factor (TNF) was examined. The amount of TNF in BALF increased significantly 2 hr after exposure to LPS. The inhalation of murine recombinant TNF-α (5 × 10<sup>4</sup> u/ml) resulted in bronchial hyperreactivity in guinea pigs. ONO-1078 (10mg/kg, p.o.) inhibited the increase of LPS-induced TNF in BALF, but ICI-204,219 (10 mg/kg, p.o.) had no effect. These results suggest that TNF plays an important role in the onset of LPS-induced bronchial hyper-reactivity, and that ONO-1078 inhibits the LPS-induced airway hyperreactivity probably due to the inhibition of TNF production.</p></div>","PeriodicalId":20653,"journal":{"name":"Prostaglandins","volume":"52 6","pages":"Pages 447-461"},"PeriodicalIF":0.0000,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0090-6980(96)00126-8","citationCount":"10","resultStr":"{\"title\":\"Cysteinyl leukotrienes do not mediate lipopolysaccharide-induced airway hyperresponsiveness in guinea pigs\",\"authors\":\"Takashi Uno, Hiroyuki Tanaka, Hiroichi Nagai\",\"doi\":\"10.1016/S0090-6980(96)00126-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Inhalation of bacterial lipopolysaccharide (LPS) by guinea pigs caused bronchial hyperreactivity to acetylcholine with a peak at 2 hr after exposure. Exposure to 0.01% LPS for 30 min resulted in an elevation of cysteinyl leukotrienes (cys-LTs) content in bronchoalveolar lavage fluid (BALF) which was obtained 1 hr after LPS exposure. The cys-LTs antagonist, ONO-1078 (10 mg/kg, p.o.), significantly inhibited LPS-induced bronchial hyperreactivity, but ICI-204,219 (10 mg/kg, p.o.), another cys-LT antagonist, did not. Each dose employed in the present study was sufficient to inhibit LTD<sub>4</sub> induced broncho-constriction in guinea pigs. In order to investigate the inhibitory mechanism of ONO-1078, the effect on the LPS-induced production of tumor necrosis factor (TNF) was examined. The amount of TNF in BALF increased significantly 2 hr after exposure to LPS. The inhalation of murine recombinant TNF-α (5 × 10<sup>4</sup> u/ml) resulted in bronchial hyperreactivity in guinea pigs. ONO-1078 (10mg/kg, p.o.) inhibited the increase of LPS-induced TNF in BALF, but ICI-204,219 (10 mg/kg, p.o.) had no effect. These results suggest that TNF plays an important role in the onset of LPS-induced bronchial hyper-reactivity, and that ONO-1078 inhibits the LPS-induced airway hyperreactivity probably due to the inhibition of TNF production.</p></div>\",\"PeriodicalId\":20653,\"journal\":{\"name\":\"Prostaglandins\",\"volume\":\"52 6\",\"pages\":\"Pages 447-461\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1996-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/S0090-6980(96)00126-8\",\"citationCount\":\"10\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostaglandins\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0090698096001268\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostaglandins","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0090698096001268","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Cysteinyl leukotrienes do not mediate lipopolysaccharide-induced airway hyperresponsiveness in guinea pigs
Inhalation of bacterial lipopolysaccharide (LPS) by guinea pigs caused bronchial hyperreactivity to acetylcholine with a peak at 2 hr after exposure. Exposure to 0.01% LPS for 30 min resulted in an elevation of cysteinyl leukotrienes (cys-LTs) content in bronchoalveolar lavage fluid (BALF) which was obtained 1 hr after LPS exposure. The cys-LTs antagonist, ONO-1078 (10 mg/kg, p.o.), significantly inhibited LPS-induced bronchial hyperreactivity, but ICI-204,219 (10 mg/kg, p.o.), another cys-LT antagonist, did not. Each dose employed in the present study was sufficient to inhibit LTD4 induced broncho-constriction in guinea pigs. In order to investigate the inhibitory mechanism of ONO-1078, the effect on the LPS-induced production of tumor necrosis factor (TNF) was examined. The amount of TNF in BALF increased significantly 2 hr after exposure to LPS. The inhalation of murine recombinant TNF-α (5 × 104 u/ml) resulted in bronchial hyperreactivity in guinea pigs. ONO-1078 (10mg/kg, p.o.) inhibited the increase of LPS-induced TNF in BALF, but ICI-204,219 (10 mg/kg, p.o.) had no effect. These results suggest that TNF plays an important role in the onset of LPS-induced bronchial hyper-reactivity, and that ONO-1078 inhibits the LPS-induced airway hyperreactivity probably due to the inhibition of TNF production.