Anti-inflammatory effects of zileuton in a subpopulation of allergic asthmatics
Anti-inflammatory effects of zileuton in a subpopulation of allergic asthmatics
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DOI：
10.1164/ajrccm.161.4.9904026
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发表时间：
2000-04-01
影响因子：
24.7
通讯作者：
Bleecker, ER
中科院分区：
文献类型：
--
作者：
Hasday, JD;Meltzer, SS;Bleecker, ER
The objective of this study was to determine the effects of allergen exposure on leukotriene generation and inflammation within the airways of allergic asthmatics and evaluate the effects of the 5-lipoxygenase inhibitor zileuton on these responses. We measured leukotriene-B-4 (LTB4) and LTC4/D-4/E-4 inflammatory cytokine mediators, and cellular responses in bronchoalveolar lavage fluid (BALF) before and 24 h after segmental ragweed antigen challenge in 18 asthmatic subjects at baseline. Before initiating therapy with the 5-lipoxygenase inhibitor or placebo, only nine of 18 asthmatic subjects had a significant increase (234 +/- 102-fold, mean +/- SE) in BALF LTC4/D-4/E-4 levels 24 h after segmental antigen challenge, whereas leukotriene levels were essentially unchanged (1.14 +/- 0.22-fold) in the other nine subjects. The high LT producers also had higher postantigen BALF levels of LTB4, total protein, IL-5, IL-6, TNF-alpha, and recovery of more eosinophils than the low LT producers. Treatment with the 5-lipoxygenase inhibitor zileuton reduced postantigen BALF eosinophil count by 68% in the high LT producers, but had no detectable effect on BALF composition in the low LT producers. These data suggest that leukotriene inhibition may be more effective in a subset of asthmatics in whom leukotrienes are a major contributory factor in causing allergic inflammation.
