EFFECT OF INDOMETHACIN ON LEUKOTRIENE4-INDUCED HISTAMINE HYPERRESPONSIVENESS IN ASTHMATIC SUBJECTS
EFFECT OF INDOMETHACIN ON LEUKOTRIENE4-INDUCED HISTAMINE HYPERRESPONSIVENESS IN ASTHMATIC SUBJECTS
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DOI：
10.1164/ajrccm/146.6.1506
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发表时间：
1992-12-01
期刊：
影响因子：
--
通讯作者：
LEE, TH
中科院分区：
文献类型：
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作者：
CHRISTIE, PE;HAWKSWORTH, R;LEE, TH
在 8 名轻度哮喘受试者中评估了吲哚美辛对 LTE4 增强气道组胺反应能力的影响。受试者在三对不同的研究日前往实验室，进行乙酰甲胆碱或 LTE4 吸入挑战，并在 4 小时和 7 小时后测量气道对组胺的反应。一对开放的研究日之后是一对服用安慰剂或吲哚美辛胶囊的研究日。使比气道电导 (PD35 SGaw) 下降 35% 的激动剂剂量是通过对数剂量反应曲线进行线性插值获得的。吲哚美辛治疗不影响基线 SGaw 或乙酰甲胆碱气道反应性。然而，吲哚美辛显着抑制 LTE4 诱导的组胺高反应性。在开放研究日和安慰剂研究日，LTE4 对组胺反应性的最大增强分别为 4.1 +/- 0.9（平均值 +/- SEM）和 5.7 +/- 1.2（p = 0.36）。吲哚美辛治疗日的最大增强为 1.68 +/- 0.46，与安慰剂治疗日相比显着下降 (p = 0.02)。这表明 LTE4 诱导的组胺反应性增强部分是由环氧合酶途径衍生产物介导的。
The effect of indomethacin on the capacity of LTE4 to enhance airway histamine responsiveness was evaluated in eight mild asthmatic subjects. Subjects attended the laboratory on three separate pairs of study days when inhalation challenges with methacholine or LTE4 were performed and the airway responses to histamine were measured 4 and 7 h later. An open pair of study days was followed by a pair of study days during ingestion of either placebo or indomethacin capsules. The dose of agonist that produced a 35% fall in specific airways conductance (PD35 SGaw) was obtained by linear interpolation from the logarithmic dose-response curve. Indomethacin treatment did not affect baseline SGaw or methacholine airway responsiveness. However, indomethacin significantly inhibited LTE4-induced histamine hyperresponsiveness. Maximum enhancement of histamine responsiveness by LTE4 on the open and placebo study days was 4.1 +/- 0.9- (mean +/- SEM) and 5.7 +/- 1.2-told, respectively (p = 0.36). Maximal enhancement on the indomethacin day was 1.68 +/- 0.46, and this was significantly decreased compared with that on the placebo day (p = 0.02). This suggests that LTE4-induced enhanced responsiveness to histamine is mediated in part by cyclooxygenase pathway-derived products.