Indomethacin and FPL-57231 inhibit antigen-induced airway hyperresponsiveness in sheep.
Indomethacin and FPL-57231 inhibit antigen-induced airway hyperresponsiveness in sheep.
复制标题
Indomethacin 和 FPL-57231 可抑制绵羊抗原诱导的气道高反应性。
DOI：
10.1152/jappl.1986.61.3.864
复制
发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Abraham,WM
中科院分区：
文献类型：
--
作者：
Lanes,S;Stevenson,JS;Codias,E;Hernandez,A;Sielczak,MW;Wanner,A;Abraham,WM
我们比较了抗原诱导的气道高反应性（AHR）的发展后24小时的挑战与猪蛔虫抗原在过敏性绵羊急性（n = 7）和双重（n = 7）气道反应，然后试图修改此AHR。通过测量使比肺阻力（sRL）增加150%所需的卡巴胆碱剂量（即，PC150）。随后，用抗原攻击绵羊，并在预定时间测量sRL，以记录是否存在迟发应答。24小时后重新测定PC 150，然后进行支气管肺泡灌洗（BAL）以评估炎症。只有双重应答者发生AHR（PC 150降低，P <0.05）。两组间BAL无显著差异。然后，在不同的情况下（大于或等于3周），用安慰剂、吲哚美辛（2 mg/kg iv）或白三烯拮抗剂FPL-57231（30 mg吸入）预处理6例双重应答者。这两种药物均不显著影响对抗原的急性反应。只有FPL预处理阻断晚期反应，但两种药物均在24 h后阻断抗原诱导的AHR。24 h BAL显示无显著差异。这些结果表明，只有双重应答者在抗原攻击后24小时发展AHR。这种AHR似乎与sRL的晚期增加或肺部炎症的严重程度无关。AHR似乎是敏感的药物，干扰早期释放或行动的环氧合酶和脂氧合酶代谢物的双重反应。
We compared the development of antigen-induced airway hyperresponsiveness (AHR) 24 h after challenge with Ascaris suum antigen in allergic sheep with acute (n = 7) and with dual (n = 7) airway responses and then attempted to modify this AHR. Cholinergic airway responsiveness was determined by measuring the carbachol dose required to increase specific lung resistance (sRL) 150% (i.e., PC150). Subsequently the sheep were challenged with antigen and sRL was measured at predetermined times to document the presence or absence of a late response. PC150 was redetermined 24 h later followed by bronchoalveolar lavage (BAL) to assess inflammation. Only dual responders developed AHR (PC150 decreased, P less than 0.05). There were no significant differences in BAL between the two groups. Six dual responders were then, on separate occasions (greater than or equal to 3 wk), pretreated with placebo, indomethacin (2 mg/kg iv), or a leukotriene antagonist, FPL-57231 (30 mg inhaled). Neither agent significantly affected the acute response to antigen. Only FPL pretreatment blocked the late response, but both agents blocked the antigen-induced AHR 24 h later. BAL at 24 h showed no significant differences. These results indicate that only dual responders develop AHR 24 h after antigen challenge. This AHR appears independent of the late increase in sRL or the severity of pulmonary inflammation. AHR appears to be sensitive to agents that interfere with the early release or actions of cyclooxygenase and lipoxygenase metabolites in dual responders.